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PubMed2026

Transcriptomic insights into temperature regulation of proliferation and differentiation in skeletal muscle cells of Nibea albiflora.

Myogenesis involves sequential stages of muscle satellite cell activation, myoblast proliferation, differentiation, and fusion into multinucleated myotubes. Teleost muscle exhibits indeterminate growth and is highly sensitive to environmental temperature, yet the underlying mechanisms by which temperature regulate proliferation and differentiation remain poorly understood. In this study, we established a primary skeletal muscle cell culture from the yellow drum (Nibea albiflora), an economically important marine fish, and integrated morphological observations with comparative transcriptomics analysis to characterize cellular and molecular responses at 28 °C and 20 °C during both proliferation and differentiation stages. Phenotypic analysis revealed that 28 °C significantly enhanced both myoblast proliferation and myogenic differentiation ability compared with 20 °C. Transcriptomic profiling revealed that at 28 °C, differentiation upregulated extracellular matrix(ECM) organization, calcium signaling, and sarcomere assembly, while proliferation enhanced focal adhesion, growth factor signaling, and lipid metabolism. At 20 °C, differentiation was characterized by glutathione metabolism, and ferroptosis, while proliferation involved cytokine-cytokine receptor interaction and negative regulation of signal transduction. Core myogenic regulatory factors (MRFs), particularly myogenin, were strongly upregulated at 28 °C during the differentiation stage, serving as an internal control. Based on these findings, we propose a testable model that elevated temperature coordinates Ca2+-dependent MRF activation with ECM-integrin signaling to drive sarcomere assembly and muscle growth. Key differentially expressed genes (DEGs) regulating myogenesis in N. albiflora were also identified. This study provides a mechanistic framework for temperature adaptation in teleost skeletal muscle and identifies candidate genes for functional validation and marker-assisted selection, as well as a rationale for temperature management strategies to improve aquaculture yield of N. albiflora.

Animals↗
PubMed2026

PIEZO1 Mediates Myoblast Proliferation Under Simulated Microgravity.

Skeletal muscle atrophy is a major health risk of prolonged spaceflight, yet how microgravity reshapes muscle cells through mechanotransduction remains poorly understood. Here, we examined the mechanosensitive cation channel PIEZO1 in myoblast proliferation under simulated microgravity. Using a two-dimensional clinostat combined with Hi-C-based 3D genomics, transcriptomics, and functional assays, we found that simulated microgravity promotes C2C12 myoblast proliferation and upregulates Piezo1. Piezo1 mRNA knockdown reduced both proliferation and depolarization-induced Ca2 + influx, each partially restored under simulated microgravity, consistent with PIEZO1 being a central mediator of the response. Simulated microgravity also drove extensive 3D genome reorganization alongside changes in proliferation-related gene expression. Integrating chromatin architecture with transcriptomics, we found that PIEZO1 inhibition increased Elavl2 mRNA expression, PIEZO1 activation suppressed Elavl2 mRNA expression, and Elavl2 mRNA knockdown enhanced cell proliferation. These findings define a PIEZO1-ELAVL2 mechanotransduction axis, coupled to 3D chromatin remodeling, that regulates myoblast proliferation under simulated microgravity, and thus may be a target for countering spaceflight-associated muscle dysfunction.

Cell Proliferation↗
PubMed2026

Colitogenic Environment Suppresses Notch/Mechanistic Target of Rapamycin-Mediated Epithelial Proliferation to Promote Goblet Cell Differentiation in the Colon.

Epithelial barrier dysfunction is a hallmark of inflammatory bowel diseases; however, the mechanisms underlying such impairment remain incompletely understood. In the present study, a dextran sulfate sodium-induced colitis model was used to investigate how the inflammatory environment damages the intestinal mucosa. The results demonstrated that colitogenic ambiance enhances intestinal epithelial cell death, delays epithelial cell proliferation, and exacerbates mucosal erosion. Unexpectedly, this work identified a previously unrecognized role for Notch signaling in mediating these effects. Specifically, the colitogenic milieu reduces Notch/mechanistic target of rapamycin complex 1 (mTORC1)-mediated intestinal epithelial cell proliferation to promote goblet cell differentiation. Chemical activation of Notch signaling stimulated intestinal epithelial cell proliferation and reduced goblet cell differentiation in the colitic mucosa, further aggravating mucosal damage. Conversely, inhibition of Notch or mTORC1 signaling during mucosal repair reduced intestinal epithelial cell proliferation and enhanced goblet cell differentiation, corroborating the implication of Notch and mTORC1 signaling in both processes. Collectively, these findings uncover a context-dependent role for the Notch-mechanistic target of rapamycin axis in regulating intestinal epithelial cell proliferation and differentiation in the colitic mucosa and suggest that its targeted modulation may hold therapeutic potential in inflammatory bowel diseases.

Animals↗
PubMed2026

Intestinal organoid screen reveals that Bacillus velezensis PGM541 promotes epithelial proliferation via its metabolite butyric acid.

BACKGROUND: Probiotics have been widely used for the regulation of intestinal health. Current screening methods for probiotics typically rely on animal or two-dimensional cell models. In this study, we employed intestinal organoids to identify a candidate probiotic strain. Furthermore, we investigated the potential mechanisms through which this strain and its active metabolites exert their effects, thereby evaluating the efficacy of this screening approach. RESULTS: Firstly, candidate probiotic strain PGM541 was identified from a porcine-derived Bacillus library by assessing organoid viability. Subsequently, to validate the organoid screening reliability, the potential mechanism of strain PGM541 on the intestinal epithelium was investigated; it was found to exhibit probiotic functions by regulating cell proliferation in both in vitro organoid and in vivo piglet models. Furthermore, organoid screening combined with metabolomic analysis identified butyric acid (BA) as the key bioactive metabolite responsible for driving epithelial proliferation. Whole-genome and transcriptomic analyses revealed the biosynthetic pathway of BA in strain PGM541. Importantly, BA receptor blockade experiments directly confirmed that BA enhances epithelial proliferation via interaction with the FFAR2 receptor, thereby validating its functional activity. Additionally, strain PGM541 exhibited protective effects against dextran sulfate sodium (DSS)-induced colitis, further validating the effectiveness of the intestinal organoid platform for probiotic screening. CONCLUSIONS: The probiotic strain PGM541, which was screened using intestinal organoids, promotes intestinal epithelial cell proliferation via its metabolite BA activating the FFAR2 receptor. These findings demonstrate that the intestinal organoid model serves as an effective platform for both preliminary probiotic screening and mechanistic investigation. Video Abstract.

Animals↗
PubMed2026

PDE4DIP-Derived MMG8 Supports Proliferation, Migration, and Tumor Growth in Hepatocellular Carcinoma Models.

BACKGROUND: PDE4DIP encodes a scaffold protein that has been implicated in compartmentalized signaling and cytoskeletal organization, but the role of its myomegalin variant 8 (MMG8) isoform in hepatocellular carcinoma (HCC) remains unclear. To address this gap, we examined PDE4DIP expression in public HCC datasets and investigated the functional role of MMG8 in HCC models. METHODS: PDE4DIP expression was analyzed in The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort and two Gene Expression Omnibus (GEO) cohorts (GSE14520, GSE36376). MMG8 function was assessed in Huh7 cells using siRNA-mediated knockdown and in Hepa1-6 cells using lentiviral Clustered Regularly Interspaced Short Palindromic Repeats - CRISPR-associated protein 9 (CRISPR-Cas9)-mediated knockout. Cell proliferation in MMG8-KD Huh7 cells and MMG8-KO Hepa1-6 cells was assessed using Cell Counting Kit-8 (CCK-8) assays, while Huh7 cell migration was evaluated using Transwell assays. Tumor growth was assessed using a murine subcutaneous tumor model. Immunohistochemical staining for Ki67 and cleaved caspase-3 was employed to assess tumor cell proliferation and apoptosis-associated changes, respectively. Gene set enrichment analysis was performed in TCGA-LIHC tumors stratified based on PDE4DIP expression. RESULTS: PDE4DIP expression differed between tumor and non-tumor tissues across HCC cohorts, although the directionality of this difference was not uniform. MMG8 knockdown in Huh7 cells reduced proliferation and migratory activity. A single-cell-derived MMG8-KO Hepa1-6 clone exhibited reduced proliferation in vitro and formed smaller tumors in vivo, with lower Ki67 positivity but no significant difference in cleaved caspase-3 positivity between groups. In tumors from the TCGA-LIHC cohort, PDE4DIP expression was associated with distinct transcriptional programs. Specifically, PDE4DIP-high tumors presented with positive normalized enrichment score (NES) values for several metabolic pathways, whereas adhesion/extracellular matrix (ECM), cell cycle/proliferation, and translation/ribosome-related pathways exhibited negative NES values. CONCLUSIONS: These findings support a functional contribution of MMG8 to proliferative, migratory, and tumor-growth phenotypes in the tested HCC models. Bulk gene-level PDE4DIP expression in human tumors was associated with context-dependent transcriptional states and should not be interpreted as a direct surrogate for MMG8 function.

Liver Neoplasms↗
PubMed2026

PDZ-binding kinase promotes ovarian cancer cell proliferation and invasion via CCNB1 regulation.

BACKGROUND: Ovarian cancer is one of the most lethal gynecological malignancies, characterized by late diagnosis, frequent recurrence, and high mortality. PDZ-binding kinase (PBK), a serine/threonine kinase of the mitogen-activated protein kinase kinase (MAPKK) family, has been implicated in the tumorigenesis of multiple cancers, yet its role in ovarian cancer remains incompletely characterized. This study aimed to investigate the effect of PBK on the proliferation and invasion of ovarian cancer cells. METHODS: The expression of PBK and cyclin B1 (CCNB1) in normal ovarian tissues and ovarian cancer tissues was analyzed using online databases including Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Kaplan-Meier Plotter. Clinical tissue specimens were collected to detect the expression of PBK and CCNB1 by immunohistochemistry. Quantitative real-time polymerase chain reaction (PCR) was performed to detect PBK messenger RNA (mRNA) expression levels in clinical specimens and cell lines. Western blot was used to detect PBK protein expression in ovarian cancer cell lines. ES2 and A2780 cells with higher PBK expression were selected to construct PBK knockdown cell lines using lentiviral interference vectors. Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) assay were performed to explore the effect of PBK knockdown on cell proliferation. Transwell assay was used to investigate the effect on cell invasion. The Cancer Genome Atlas (TCGA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized to analyze PBK-related pathways and predict CCNB1 as the gene most closely related to PBK. RESULTS: PBK was significantly overexpressed in ovarian cancer tissues and cell lines compared with normal controls, and high PBK expression was associated with poor overall survival (OS) and progression-free survival (PFS). Knockdown of PBK expression inhibited the proliferation, colony formation, and invasion of ovarian cancer cells. Bioinformatics analysis revealed that CCNB1 was significantly overexpressed in ovarian cancer and high CCNB1 expression was associated with poor OS. CCNB1 was also significantly highly expressed in ovarian cancer tissues as validated by immunohistochemistry and was associated with lymph node metastasis. PBK and CCNB1 expression showed a significant positive correlation in TCGA ovarian cancer datasets. Knockdown of PBK inhibited CCNB1 expression in ovarian cancer cells. CONCLUSIONS: PBK promotes ovarian cancer cell proliferation and invasion. PBK knockdown leads to CCNB1 downregulation. These findings suggest that CCNB1 contributes to PBK-mediated oncogenic effects and identify the PBK-CCNB1 axis as a potential therapeutic target for ovarian cancer treatment.

PDZ-binding kinase (PBK)↗
PubMed2025

Baculovirus enhances arginine uptake and induces mitochondrial autophagy to promote viral proliferation.

As obligatory intracellular parasites, viruses must rely on metabolic reprogramming of host cells to meet their replication needs. Baculovirus is an important biopesticide and a vector for the preparation of biological products. In addition, one of its representative species, Bombyx mori nucleopolyhedrovirus (BmNPV-Baculoviridae), also causes huge losses to the insect industry. In our previous study, amino acid metabolism has been found to play a crucial role in the BmNPV infection process. However, the mechanisms by which BmNPV reprograms host amino acid metabolism remains unclear. In fact, current insights in the importance of amino acid metabolism are limited to the impact of glutamine on viral infection. Therefore, unraveling the mechanism of amino acid metabolism reprogramming induced by baculovirus would advance this field of research to a great extent. In this study, targeted metabolomics revealed that the preferred amino acids of BmNPV budded virus (BV) include arginine, lysine, proline, isoleucine, histidine and others. In addition, most of the viral amino acids were found to be increased in the hemolymph of BmNPV infected silkworms at the later stage of infection, especially arginine, valine, phenylalanine and others. Furthermore, the importance of arginine for BmNPV proliferation was validated. Next, we confirmed that the expression of the arginine transporter Slc7a6 was strongly induced by BmNPV infection and that Slc7a6 could promote arginine uptake to support BmNPV proliferation in host cells. Moreover, using Slc7a6 knockout cells which eliminate extracellular arginine uptake, we confirmed that BmNPV could induce mitochondrial autophagy, thereby supplementing intracellular arginine and providing necessary amino acids for BmNPV proliferation. Overall, these findings support a model in which baculovirus (BmNPV) enhances the uptake of exogenous amino acids by inducing the expression of amino acid transporters and activating autophagy of organelles to maintain intracellular amino acid levels, thereby facilitating virus proliferation.

Animals↗
PubMed2025

Clinicopathologic, Immunohistochemical, and Molecular Analysis of Primary Ovarian Carcinoid Tumors With Correlation of Ki67 Proliferation Index With Patient Outcomes.

Primary ovarian carcinoid tumors (pOCTs) are a rare subset of ovarian neoplasms resembling well-differentiated neuroendocrine tumors (NETs) arising in the gastrointestinal tract. Unlike NETs at other anatomic sites, the use of proliferation markers, such as mitotic count and Ki67 proliferation index, is not well established in the classification of these tumors. In this study, we describe the clinicopathologic, immunohistochemical, and molecular characteristics of pOCTs and correlate mitotic count and Ki67 index with patient outcomes. In our series of 23 pOCTs, most cases were associated with at least 1 other ovarian neoplasm (19/23; 82.6%), most often a mature teratoma or struma ovarii (each 43.5%; 10/23). All 23 cases (100%) expressed synaptophysin, whereas 87.0% (20/23) expressed chromogranin. Frequent staining with TTF-1 and CDX2 (33.3% and 83.3%, respectively) was also observed. Targeted exome sequencing was performed in 14 cases, which identified no recurrent NET-associated mutations or novel mutations in pOCTs. Most pOCTs presented as stage IA disease (13/23; 56.5%), of which 6 had Ki67 indices >3% (46.2%; 6/13). There were 6 cases of stage IC disease (26.0%), which exhibited a variable Ki67 index (range: 1.2%-35.6%). Extraovarian spread was noted in 4 cases (17.4%), with 3 cases having Ki67 indices >3% (range: 1.0%-58.8%). Local recurrence occurred in 1 case (4.3%) with pelvic sidewall involvement at diagnosis and a Ki67 index of 58.8%. Follow-up, ranging from 3 to 153 months (median: 55.5 months), showed no disease-related deaths. We combined our findings with 16 previously published cases of pOCTs and found that cases with >20 mitoses per 2 mm2 had the highest rate of recurrence. Cases with Ki67 indices ≥ 7.5% were associated with worse overall and disease-free survival. Overall, our findings reaffirm the indolent nature of most pOCTs, although disease recurrence and aggressive behavior can occur, particularly in cases with elevated proliferation indices.

Humans↗
PubMed2026

Mechanistic insights into CAR-mediated repression of the HNF4α-FABP1 axis and inhibition of HepG2 cell proliferation.

The constitutive androstane receptor (CAR) modulates the transcription of numerous genes involving drug metabolism, energy homeostasis, and cell proliferation. While rodent studies suggest an oncogenic role for murine CAR in liver cancer development, emerging evidence indicates that human CAR (hCAR) may exhibit a tumor-suppressive role in hepatocellular carcinoma; notably, overexpressing hCAR suppresses human hepatoma cell proliferation. Yet, the molecular mechanisms whereby hCAR suppresses hepatoma cell proliferation are poorly understood. Our recent RNA-seq analysis of human hepatoma cells revealed that fatty acid binding protein 1 (FABP1), a pleiotropic modulator of lipid metabolism and cancer progression, was a top gene downregulated by hCAR. Here, we report a molecular mechanism whereby hCAR downregulates FABP1 expression by modulating HNF4α signaling. Knocking down hCAR expression in a HepG2-hCAR stable cell line restores the suppressed expression of FABP1 and HNF4α, while knocking down HNF4α alone is sufficient to suppress FABP1 expression. Luciferase reporter assays revealed concentration-dependent hCAR suppression of HNF4α-mediated FABP1 transactivation. This inhibitory crosstalk between hCAR and HNF4α was further confirmed by chromatin immunoprecipitation assays, where hCAR decreased HNF4α occupancy of the FABP1 promoter. Mechanistically, hCAR inhibits HNF4α expression by prompting deacetylation of histone H3 in the HNF4α P1 enhancer region, resulting in a repressive chromatin configuration and reduced HNF4α transcription. Furthermore, overexpressing FABP1 partially rescued hCAR-suppressed cell growth. Collectively, these results uncover the hCAR-HNF4α-FABP1 axis as a novel mechanism underlying hCAR-mediated gene repression.

Humans↗
PubMed2026

KLF5 promotes proliferation, migration, and autophagy-/EMT‑associated molecular changes in lens epithelial cells via transcriptional activation of THBS1 in traumatic cataract.

PURPOSE: Traumatic cataract is a common blinding eye disease after ocular trauma, and its pathogenesis is closely related to lens epithelial cell dysfunction, while the definite molecular regulatory mechanism between upstream transcription factor and downstream target gene remains poorly clarified. This study aimed to clarify the role and molecular mechanism of the krüppel-like factor 5 (KLF5)/ thrombosponin 1 (THBS1) axis in regulating proliferation, migration, epithelial-mesenchymal transition and autophagy of lens epithelial cells in traumatic cataract, and to explore its potential clinical therapeutic value. METHODS: The GSE295383 dataset in the gene expression omnibus (GEO) database was downloaded, and the differentially expressed genes (DEGs) were screened by linear models for microarray data (limma) package of R language. Combined with Weighted gene co-expression network analysis (WGCNA), the gene co-expression network was constructed and the key modules were screened. Gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) combined with human transcription factor target (hTFtarget) and JASPAR databases were used to predict the upstream transcription factors of THBS1. Subsequently, SRA01/04 cells were induced with transforming growth factor-beta 2 (TGF-β2) to construct a cataract cell model. RESULTS: THBS1 and KLF5 were highly expressed in LECs exposed to TGF-β2. KLF5 could activate THBS1 transcription by binding to THBS1 promoter - 174 to -165 sites. Knockdown of THBS1 inhibited TGF-β2-induced viability, proliferation, migration, and altered the expression of epithelial-mesenchymal transition (EMT)- and autophagy-related markers in LECs. Knockdown of KLF5 downregulated THBS1 expression and produced a similar inhibitory effect, while overexpression of THBS1 reversed the effect of KLF5 knockdown. CONCLUSIONS: This study demonstrated that KLF5 promoted the proliferation, migration, and EMT‑associated molecular changes of LECs in traumatic cataract through transcriptional activation of THBS1, and regulated the expression of autophagy‑related markers in LECs, suggesting that KLF5/THBS1 axis might be a potential target for the treatment of traumatic cataract.

Cataract↗
PubMed2026

ERP44 Is Associated With Poor Prognosis and Promotes Proliferation and Temozolomide Resistance in Lower-grade Glioma.

BACKGROUND/AIM: Endoplasmic reticulum resident protein 44 (ERP44), a protein disulfide isomerase family member, has been implicated in tumor biology, but its role in lower-grade glioma (LGG) remains unclear. This study investigated the prognostic significance and biological function of ERP44 in LGG, focusing on proliferation and temozolomide (TMZ) resistance. MATERIALS AND METHODS: ERP44 expression, clinicopathological associations, and prognostic value were analyzed using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA) datasets. Time-dependent receiver operating characteristic (ROC) curves, Cox regression, and a prognostic nomogram were constructed. Differential expression, Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) enrichment, immune infiltration, and drug sensitivity analyses were performed. Functional validation was conducted in SW1088 and SW1783 cells using shRNA-mediated ERP44 knockdown, followed by RT-qPCR, western blotting, CCK-8, colony formation, and TMZ IC50 assays. Subcutaneous xenograft models with or without TMZ treatment were used for in vivo validation. RESULTS: ERP44 was markedly upregulated in LGG and associated with higher WHO grade, IDH wildtype status, 1p/19q non-codeletion, and poor survival in TCGA and CGGA cohorts. ERP44 showed strong prognostic performance and improved risk stratification in a multivariable nomogram. Enrichment analyses linked high ERP44 expression to immune/inflammatory pathways and reduced neuronal functional signatures. ERP44 positively correlated with immune infiltration, proliferation/stemness markers, and predicted TMZ resistance, while its knockdown inhibited proliferation and colony formation, reduced TMZ IC50, suppressed xenograft growth, enhanced TMZ efficacy, and decreased Ki67 positivity. CONCLUSION: ERP44 is a prognostic biomarker that promotes LGG proliferation and TMZ resistance, suggesting its potential as a therapeutic target.

Humans↗
PubMed2026

Thyroxine enhances breast cancer cell survival and proliferation via TRβ1-Dependent PI3K/AKT signaling.

Thyroid hormones (TH) influence tumor biology through both genomic and non-genomic mechanisms. Specifically, thyroxine (T4) activates signaling pathways linked to cancer progression through interactions with nuclear receptors, such as TRβ1, and membrane receptors, including integrin αvβ3. Nevertheless, the precise role of T4 in breast cancer cell behavior and its underlying molecular mechanisms remain incompletely understood. The effects of physiological concentrations of T4 (10-9 M) on proliferation, cell viability, apoptotic signaling, and activation of intracellular pathways were evaluated in human mammary cell lines. Tumor cell lines (MCF-7 and MDA-MB-231) and the non-tumor mammary epithelial cell line MCF-10A were treated with T4 alone or in combination with the thyroid hormone receptor antagonist 1-850. Cell proliferation was measured using the MTT assay, and viability was determined by trypan blue exclusion. Protein expression and signaling pathways were analyzed by Western blot, including assessment of apoptotic markers (caspases, PARP, Bax, Bcl-2), PCNA, steroid hormone receptors, and signaling mediators such as PI3K, AKT, and ERK. Immunocytochemistry was used to evaluate TRβ1, integrin αvβ3, and Ki67 expression. T4 treatment increased proliferation and survival in hormone-sensitive tumor cells, accompanied by modulation of apoptosis-related proteins and activation of the PI3K/AKT pathway. The antagonist 1-850 selectively attenuated TRβ1-dependent effects, enabling distinction between genomic and integrin-mediated mechanisms. These effects were observed exclusively in hormone-sensitive tumor cells. These findings support a role for T4 in breast cancer progression and identify TH-related signaling pathways as potential therapeutic targets.

Apoptosis↗
PubMed2024

Transient Zn2+ deficiency induces replication stress and compromises daughter cell proliferation.

Cells must replicate their genome quickly and accurately, and they require metabolites and cofactors to do so. Ionic zinc (Zn2+) is an essential micronutrient that is required for hundreds of cellular processes, including DNA synthesis and adequate proliferation. Deficiency in this micronutrient impairs DNA synthesis and inhibits proliferation, but the mechanism is unknown. Using fluorescent reporters to track single cells via long-term live-cell imaging, we find that Zn2+ is required at the G1/S transition and during S phase for timely completion of S phase. A short pulse of Zn2+ deficiency impairs DNA synthesis and increases markers of replication stress. These markers of replication stress are reversed upon resupply of Zn2+. Finally, we find that if Zn2+ is chelated during the mother cell's S phase, daughter cells enter a transient quiescent state, maintained by sustained expression of p21, which disappears upon reentry into the cell cycle. In summary, short pulses of mild Zn2+ deficiency in S phase specifically induce replication stress, which causes downstream proliferation impairments in daughter cells.

Zinc↗
PubMed2026

A model of cellular proliferation and mitochondrial biogenesis predicts prognosis and immunotherapy response in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD), which is the leading subtype of non-small cell lung cancer (NSCLC), poses considerable difficulties in accurate prognostic assessment and targeted therapeutic options. Cell proliferation-related genes (CPGs) and mitochondrial biogenesis-related genes (MBGs) play critical roles in tumor metabolic reprogramming; however, their prognostic value and molecular mechanisms in LUAD are poorly understood. This study aims to construct a CPG/MBG-based prognostic risk model for LUAD, evaluate its clinical utility in predicting prognosis and immunotherapy response, and experimentally validate the functional role of key model genes in LUAD progression. METHODS: By utilizing The Cancer Genome Atlas (TCGA)-LUAD and GSE72094 datasets, this investigation formulated a risk scoring model through differential expression screening combined with least absolute shrinkage and selection operator (LASSO)-Cox regression analysis. The molecular characteristics and clinical implications of the risk model were investigated via immune microenvironment evaluation, genomic alteration analysis, and drug sensitivity prediction. The functional contributions of key genes were further substantiated using quantitative reverse transcription polymerase chain reaction (qRT-PCR), commercial assay kits, the JC-1 fluorescent probe, the Cell Counting Kit-8 (CCK-8), Transwell invasion assays, and wound healing assays. RESULTS: A risk model based on seven CPGs and MBGs (PLK1, HMMR, CYP27A1, LDHA, NPAS2, KRT17, CIDEC) showed reliable predictive performance in both GSE72094 and the TCGA-LUAD cohorts. Enhanced tumor heterogeneity and an immunosuppressive microenvironment were observed in the high-risk group. Drug sensitivity analysis indicated that the risk model could guide personalized treatment strategies; for instance, high-risk patients showed increased susceptibility to agents such as docetaxel and 5-fluorouracil. In vitro experiments demonstrated that the key gene CIDEC exhibited upregulated expression in LUAD tissues and cells. Knockdown of CIDEC led to enhanced cellular energy metabolism and increased mitochondrial membrane potential, while also effectively suppressing cell invasion, proliferation, and migration. CONCLUSIONS: The established MBGs/CPGs prognostic model provides a novel tool for stratified treatment planning in LUAD, underscoring the crucial roles of cellular proliferation and mitochondrial biogenesis in tumor progression. Functional validation of CIDEC offers experimental support for the development of potential therapeutic strategies.

Lung adenocarcinoma (LUAD)↗
PubMed2026

Multi-level Transcriptomic and Machine-learning Analyses Identify MZT1 as a Proliferation-associated Prognostic Marker in Lung Adenocarcinoma.

BACKGROUND/AIM: Lung adenocarcinoma (LUAD) exhibits substantial molecular heterogeneity and variable clinical outcomes, highlighting the need for biomarkers that reflect core tumor biological processes. Centrosome-associated proteins regulate mitotic fidelity and genome stability, yet their roles in LUAD remain incompletely defined. In this study, we systematically characterized mitotic spindle organizing protein 1 (MOZART1; MZT1) and related family members in LUAD. MATERIALS AND METHODS: We performed integrated analyses combining bulk transcriptomic datasets, survival modeling, gene set enrichment, immune deconvolution, machine-learning based prognostic modeling, and single-cell RNA sequencing. Expression patterns and clinical associations of MZT family genes were evaluated across pan-cancer and LUAD cohorts. RESULTS: MZT family genes were consistently upregulated in tumor tissues, with MZT1 showing the most robust expression pattern. Elevated MZT1 expression was significantly associated with reduced overall survival. Functional analyses revealed coordinated activation of proliferative and genome maintenance pathways, including G2/M checkpoint regulation, E2F and MYC signaling, and DNA repair. A multivariable analysis indicated that the prognostic association of MZT1 was reduced after adjusting for canonical proliferation markers, suggesting partial overlap with established proliferation signals. The LASSO-based Cox model demonstrated stable time-dependent predictive performance at 1-, 3-, and 5-year survival. Immune analyses indicated associations between MZT1 expression and tumor microenvironmental features. Single-cell analysis showed that MZT1 expression was predominantly enriched in malignant epithelial cells and associated with proliferative cellular states. Protein-level validation supported concordance with transcriptomic findings. CONCLUSION: MZT1 is a proliferation-associated marker that integrates clinical risk, transcriptional programs, cellular heterogeneity, and predictive modeling in LUAD, providing a potential framework for biomarker development and risk stratification.

Humans↗
PubMed2023

Transient Zn2+ deficiency induces replication stress and compromises daughter cell proliferation.

Cells must replicate their genome quickly and accurately, and they require metabolites and cofactors to do so. Ionic zinc (Zn2+) is an essential micronutrient that is required for hundreds of cellular processes, including DNA synthesis and adequate proliferation. Deficiency in this micronutrient impairs DNA synthesis and inhibits proliferation, but the mechanism is unknown. Using fluorescent reporters to track single cells via long-term live-cell imaging, we find that Zn2+ is required at the G1/S transition and during S-phase for timely completion of S-phase. A short pulse of Zn2+ deficiency impairs DNA synthesis and increases markers of replication stress. These markers of replication stress are reversed upon resupply of Zn2+. Finally, we find that if Zn2+ is removed during the mother cell's S-phase, daughter cells enter a transient quiescent state, maintained by sustained expression of p21, which disappears upon reentry into the cell cycle. In summary, short pulses of mild Zn2+ deficiency in S-phase specifically induce replication stress, which causes downstream proliferation impairments in daughter cells.

Biological sciences↗
PubMed2024

Mast cells proliferate in the peri-hippocampal space during early development and modulate local and peripheral immune cells.

Brain development is a non-linear process of regionally specific epochs occurring during windows of sensitivity to endogenous and exogenous stimuli. We have identified an epoch in the neonatal rat brain defined by a transient population of peri-hippocampal mast cells (phMCs) that are abundant from birth through 2-weeks post-natal but absent thereafter. The phMCs are maintained by proliferation and harbor a unique transcriptome compared with mast cells residing in the skin, bone marrow, or other brain regions. Pharmacological activation of this population broadly increases blood-brain barrier permeability, recruits peripheral immune cells, and stunts local microglia proliferation. Examination of the post-mortem human brain demonstrated mast cells in the peri-hippocampal region of a newborn, but not an older infant, suggesting a similar developmental period exists in humans. Mast cells specifically, and early-life inflammation generally, have been linked to heightened risk for neurodevelopmental disorders, and these results demonstrate a plausible source of that risk.

Mast Cells↗
PubMed2026

Yorkie/Scalloped-OVOL-Rac1 axis controls insect wing development by promoting cell proliferation.

The regulation of organ size is a fundamental question in developmental biology, and insect wings provide a powerful model for elucidating the genetic mechanisms underlying morphogenesis. Although the conserved Hippo signaling pathway plays a central role in controlling tissue growth, its precise regulatory network during wing development remains incompletely understood. Here, we identify the zinc finger transcription factor OVOL as a critical mediator of Hippo signaling in insect wing development. We indicate that OVOL is essential for normal wing formation in both Locusta migratoria and Drosophila melanogaster, regulating cell proliferation and trichome patterning. Through transcriptomic analysis and functional validation, we further identify the small GTPase Rac1 as a key downstream effector of OVOL that promotes proliferative growth. Moreover, we find that OVOL expression is directly activated by the Yorkie/Scalloped (Yki/Sd) complex, the core transcriptional effector of the Hippo pathway, without forming a feedback loop. This regulation is mediated through a specific Sd-binding motif (GATAA) within the OVOL promoter. Importantly, Yki/Sd-induced Rac1 expression is dependent on OVOL. Collectively, our findings establish the Yorkie/Sd-OVOL-Rac1 pathway that governs insect wing development by promoting cell proliferation, providing mechanistic insights into organ size regulation in animals.

Cell proliferation↗