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PubMed2026

Unraveling the c-Myc-CASC19/HDAC1-NPM1 epigenetic axis: A novel regulatory circuitry and therapeutic target in gastric carcinogenesis.

Mounting evidence implicates long non-coding RNA cancer susceptibility candidate 19 (CASC19) in the pathogenesis of diverse malignancies. However, its functional role and molecular mechanisms in gastric cancer (GC) remain elusive. Herein, we identified a novel 717-bp transcript isoform of CASC19 in GC cells. This study aimed to delineate the biological functions and underlying mechanisms of this novel CASC19 transcript in GC pathogenesis. CASC19 was significantly upregulated in GC tissues and cell lines, correlating with adverse clinicopathological features and poor prognosis in GC patients. Functional investigations demonstrated that CASC19 overexpression potentiated GC cell proliferation, metastasis, and epithelial-mesenchymal transition, whereas CASC19 knockdown attenuated these malignant phenotypes and suppressed tumorigenesis in xenograft models. Mechanistically, CASC19 functioned as a molecular scaffold by recruiting histone deacetylase 1 (HDAC1) to the nucleophosmin 1 (NPM1) promoter. This recruitment sustained H3K27 deacetylation, thereby transcriptionally repressing NPM1 promoter activity and accelerating gastric carcinogenesis. Crucially, Depletion of HDAC1 or NPM1 partial rescued CASC19-mediated oncogenic effects. Intriguingly, the transcription factor c-Myc was found to transcriptionally activate CASC19 through direct binding to its promoter region. Collectively, our findings indicate that the c-Myc-CASC19/HDAC1-NPM1 axis acts as a potential prognostic biomarker candidate for GC and may represent a therapeutic vulnerability worthy of future investigation.

Humans↗

PubMed2026

Proteomic profiling reveals that DPP4 overexpression increases cell adhesion, inhibits cell migration, and restores androgen sensitivity in prostate cancer.

Dipeptidyl peptidase-4 (DPP4), a serine protease with both enzymatic and non-enzymatic roles, has emerged as a context-dependent modulator of tumor progression. In the present study, we investigated the expression and function of DPP4 in androgen-sensitive and castration-resistant prostate cancer (CRPC) models. Proteomic analysis of androgen-resistant prostate cells overexpressing DPP4 identified the involvement of the cellular adhesion molecules pathway. In prostate cells, lentiviral-mediated DPP4 overexpression restored androgen receptor signaling, inhibited epithelial-to-mesenchymal transition, and reduced cell migration, whereas DPP4 silencing produced the opposite effects. We demonstrate that DPP4 expression is down-regulated in CRPC cells and that treatment with capsaicin (CAP), a bioactive compound derived from red peppers, restores DPP4 expression. Moreover, DPP4 restoration by CAP suppresses prostate tumorigenesis in the TRAMP mice in vivo model of prostate cancer. Our results suggest that DPP4 could be a new target for CRPC.

Male↗

PubMed2026

Effects of phenylephrine and norepinephrine with restrictive infusion on oxygenation during one-lung ventilation for lung surgery: a randomized controlled trial.

OBJECTIVE: This study compared the effects of norepinephrine or phenylephrine combined with restrictive infusion on the oxygenation during thoracoscopic one-lung ventilation (OLV). METHODS: Ninety patients were randomly divided into three groups: the norepinephrine group (Group N), the phenylephrine group (Group P), and the control group (Group C). Arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt fraction (Qs/Qt) were measured with patients in lateral positions during two-lung ventilation (TLV) at 10 min (T1), and during OLV at 15 min (T2) and 45 min (T3). Lung tissue samples were analyzed for endothelin and COX-2 levels after surgery. RESULTS: At T3, Group P had significantly higher PaO2 and lower Qs/Qt than Groups N and C (all p < 0.05), with no significant differences between Groups N and C (all p > 0.05). Compared to T1, Groups N and C showed significantly lower PaO2 and higher Qs/Qt at T2 and T3 (all p < 0.05), with no significant differences in PaO2 and Qs/Qt at T3 compared with T2 (all p > 0.05). Group P patients had lower PaO2 and higher Qs/Qt at T2 and T3 compared to T1 (all p < 0.05), but at T3, PaO2 increased and Qs/Qt decreased compared to T2 (all p < 0.05). Lung tissue levels of endothelin and COX-2 were significantly elevated in group P compared to groups N and C (all p < 0.05). CONCLUSION: Combining phenylephrine with restrictive infusion during OLV improved oxygenation by increasing PaO2, decreasing Qs/Qt, and raising endothelin and COX-2 levels in lung tissue, thereby enhancing the HPV effect.

Humans↗

PubMed2026

Prognostic significance of NLRP-3 expression in solid cancers: a systematic review and meta-analysis.

BACKGROUND: The inflammasome is a critical immunological sensor comprised of NLRP-3, ASC, and CASPASE-1. Mutations in NLRP-3 are prevalent in inflammatory diseases. However, the role of NLRP-3 in cancer is controversial. This study investigates whether NLRP-3 expression is associated with clinical outcomes in patients with solid cancers. METHODS: PubMed (MEDLINE), Embase, Cochrane, and Google Scholar were searched for articles reporting NLRP-3 expression and disease outcome data in cancer patients. RevMan Review Manager was used to calculate pooled hazard ratios and Mantel-Haenszel pooled odds ratios. RNA sequencing datasets from the TCGA Pan-Cancer (PANCAN) were used for external validation. RESULTS: Patients with higher NLRP-3 expression showed a significant association with larger tumor size, advanced tumor grade, TNM stage, and presence of metastasis. High NLRP-3 expression has a significant association with poor OS (HR:2.12, 95% CI = 1.49-3.03), p < 0.0001) and DFS (HR:1.86, 95% CI = 1.30- 2.65, p = 0.0007). Subgroup analysis showed that higher NLRP-3 expression is associated with worse OS in head and neck cancer (HR: 2.77, 95% CI = 1.88-4.09, p < 0.00001), colorectal cancers (HR:2.14, 95% CI= 1.59- 2.87, p < 0.00001), and pancreatic cancer patients (HR: 3.19, 95% CI = 1.73-5.91, p = 0.0002). CONCLUSION: High NLRP-3 expression is associated with advanced disease and poor outcomes in many solid tumours.

Humans↗

PubMed2026

Identification and functional characterization of a novel antiviral chicken interferon-υ.

Interferons are critical mediators of antiviral immunity in vertebrates. While type IV interferon (IFN-υ) has been identified in fish and amphibians, its existence and function in chickens remained unknown. Through systematic genomic screening, we identified and cloned a novel chicken interferon gene, designated ChIFN-υ. Phylogenetic analysis placed ChIFN-υ within a distinct clade alongside zebrafish and clawed frog IFN-υ, confirming its identity as a type IV interferon, with minimal homology to classical type I, II, or III IFNs. Expression profiling revealed constitutive ChIFN-υ expression in mucosal and immune tissues of healthy chickens, exhibiting a distinct developmental shift: highest in trachea and small intestine in 1-day-old chicks, shifting to spleen and lung in 4-week-old chickens. ChIFN-υ expression was strongly upregulated following H9N2 AIV infection. Functionally, recombinant ChIFN-υ protein activated the interferon-stimulated response element (ISRE) and Mx promoter in a dose-dependent manner and significantly inhibited the replication of both vesicular stomatitis virus (VSV) and H9N2 AIV in DF-1 cells. In vivo, early treatment with exogenous ChIFN-υ significantly reduced pulmonary and tracheal viral loads and decreased oropharyngeal and cloacal virus shedding in H9N2-infected chickens. In conclusion, this study identifies and functionally characterizes the type IV interferon in chickens, elucidating the evolutionary status, regulated expression, and antiviral efficacy of ChIFN-υ. These findings highlight its potential as a candidate for developing interferon-based therapies against avian viral diseases.

Animals↗

PubMed2026

Postoperative chemoradiotherapy in Wilms tumor with concurrent lung and lymph node metastasis.

BACKGROUND: An effective treatment strategy is essential for metastatic Wilms tumor (WT) management. To improve prognostic accuracy, this study examined metastatic patterns and key prognostic factors. METHODS: Children diagnosed with WT from 2010 to 2021 were identified from the SEER database. All patients underwent chemotherapy and surgical resection. Metastatic patterns, metastasis-related predictors, and prognostic factors were evaluated. RESULTS: Of the 1040 patients analyzed, 226 (21.7%) experienced lung metastasis, 31 (3.0%) liver metastasis, 6 (0.6%) bone metastasis, and 220 (21.2%) regional lymph node metastasis. Distant metastasis was associated with a higher incidence of lymph node metastasis (OR = 1.506, 95% CI 1.346-1.685, p < 0.001). Age 3-17 years (OR = 1.933, 95% CI 1.406-2.680, p < 0.001), left-sided (OR = 1.383, 95% CI 1.016-1.890, p = 0.040), bilateral (OR = 2.303, 95% CI 1.215-4.243, p = 0.009), and tumor size ≥135 mm (OR = 2.020, 95% CI 1.481-2.749, p < 0.001) were identified as predictors of metastasis. Both lymph node (p < 0.001) and lung metastasis (p < 0.001) were high-risk factors for WT. Radiotherapy provided long-term survival benefits for the metastatic population (p = 0.027), while postoperative chemotherapy showed better outcomes than preoperative or other strategies (p < 0.001). Further analysis demonstrated that the concurrent lung and lymph node metastasis group benefited more from postoperative chemoradiotherapy, with HRs of 0.226 (p = 0.028) for overall survival and 0.255 (p = 0.048) for cancer-specific survival. CONCLUSION: WT with concurrent lung and lymph node metastasis represents a distinct and aggressive metastatic phenotype associated with a significantly poor prognosis. Postoperative chemoradiotherapy may provide superior survival benefits for this high-risk population.

Humans↗

PubMed2026

Hierarchical modeling of tumor subtypes in cell lines using large-scale genomic datasets.

Cancer cell lines (CLs) are widely used to study tumor biology and drug response, yet their translational relevance is often limited by inaccurate subtype annotations. Existing CL-tumor matching approaches are frequently constrained by flat classification schemes, weak subtype definitions, and the exclusion of normal tissue references, leading to potential confounding of tumor-specific and tissue-of-origin signals. To address these limitations, a hierarchical classification (HC) framework is presented in which CLs are aligned with patient tumors across biological resolutions, from organ to molecular subtype. Gene expression profiles from 802 CLs, 5,612 tumors from The Cancer Genome Atlas (TCGA) , and 8,939 non-cancerous tissues were integrated to separate oncogenic signals from tissue-specific signals. Node-specific features were selected using maximum relevance minimum redundancy, and balanced accuracies of 89% in cross-validation and 75%, and 80% on external datasets were achieved. Through the framework, 43 CLs were reassigned, and clinically relevant underrepresented subtypes were identified.

cancer cell lines↗

PubMed2026

Accelerated Biological Aging Increases the Risk of Head and Neck Cancer: Insights From Genetic Instruments of Epigenetic Clocks.

Epigenetic clocks are robust biomarkers of biological aging and have been associated with cancer susceptibility. However, the relationship between genetically predicted epigenetic age acceleration and head and neck cancer risk remains unclear. Using a large case-control study of 2189 head and neck squamous cell carcinoma (HNSCC) cases and 2189 age- and sex-matched controls, we investigated the associations between polygenic scores (PGSs) for multiple epigenetic clocks and HNSCC risk, and evaluated their potential causal roles using two-sample Mendelian randomization (MR). Genome-wide association study (GWAS)-identified single nucleotide polymorphisms (SNPs) associated with four epigenetic clocks (HannumAge, HorvathAge, GrimAge, and PhenoAge) were used to construct clock-specific PGSs. Logistic regression models were applied to assess associations between PGSs and HNSCC risk, while MR analyses, including inverse-variance weighted (IVW), weighted median, and MR-Egger methods, were used to infer potential causal relationships. Among the 48 epigenetic clock-associated SNPs, 12 showed nominal associations with HNSCC risk, and one variant (rs2275558 in PBX1) remained significant after Bonferroni correction (OR = 0.67, 95% CI: 0.60-0.76). PGSs for all four epigenetic clocks were higher in cases than in controls. In logistic regression analyses, each standard deviation increase in HannumAge PGS was associated with a 25% higher risk of HNSCC (OR = 1.25, 95% CI: 1.10-1.41), whereas HorvathAge, GrimAge, and PhenoAge PGSs showed weaker positive associations (ORs ranging from 1.06 to 1.10). Individuals in the highest PGS quartile for all four epigenetic clocks exhibiting 14%-25% higher risk than those in the lower three quartiles. MR analyses supported potential causal effects of genetically predicted HannumAge (IVW OR = 1.24 per SD increase, 95% CI: 1.09-1.42) and GrimAge (IVW OR = 1.23 per SD increase, 95% CI: 0.98-1.56) on HNSCC risk, with consistent estimates in weighted median analyses. Our results highlight biological aging as a potential etiologic mechanism for HNSCC and suggest that epigenetic clock-related genetic profiles may improve HNSCC risk stratification.

Humans↗

PubMed2026

Thoracic paravertebral block with different doses of liposomal bupivacaine versus ropivacaine for postoperative analgesia in single-port thoracoscopic lung surgery: a randomized clinical trial.

OBJECTIVE: To evaluate the analgesic efficacy of thoracic paravertebral block (TPVB) with different doses of liposomal bupivacaine (LB) or ropivacaine in patients undergoing single-port thoracoscopic lung surgery. METHODS: A total of 105 patients scheduled for video-assisted single-port thoracoscopic lung surgery were randomized in a 1:1:1 ratio into three groups: low-dose LB group (group LL), high-dose LB group (group HL), or ropivacaine group (group R). All received ultrasound-guided TPVB at the T5/6 level preoperatively. The primary outcome was the area under the curve (AUC) of NRS of pain at activity (AUC-aNRS) from 1 to 72 h postoperatively. Secondary outcomes included the AUC of NRS of pain at rest (AUC-rNRS) from 1 to 72 h postoperatively, NRS of pain at rest and at activity at 1, 6, 24, 48, and 72 h postoperatively, and the cumulative opioid consumption at 24, 48, and 72 h postoperatively. Additionally, postoperative recovery and adverse events were assessed. RESULTS: AUC-aNRS differed significantly among groups (p = 0.0092), with high-dose LB lower than low-dose LB (p = 0.0071), but not versus ropivacaine. No significant difference was found in AUC-rNRS (p > 0.05). The group-by-time interactions for NRS of pain at rest and at activity were not significant (p > 0.05). Cumulative opioid consumption at 24, 48, and 72 h was lower in group HL versus group LL (all p < 0.017), but not versus ropivacaine. Postoperative recovery and adverse events showed no differences (p > 0.05). CONCLUSION: LB combined with TPVB is not superior to ropivacaine for postoperative analgesia in single-port thoracoscopic lung resection.

Humans↗

PubMed2026

Alternative End Joining Dependency Imposed by miR-21-5p Defines Radiation Resistance and a Targetable Vulnerability in Oral Squamous Cell Carcinoma.

PURPOSE: Clinical control of oral squamous cell carcinoma (OSCC) is constrained by heterogeneous radiosensitivity driven by divergent DNA damage response programs. The architecture and functional contribution of alternative end joining (Alt-EJ), an error-prone DNA double-strand break (DSB) repair pathway frequently upregulated in cancer, to radiation resistance remains poorly defined. METHODS AND MATERIALS: We profiled microRNAs in radioresistant OSCC clones and performed multiomic integration across an institutional OSCC cohort, an external OSCC cohort from the Gene Expression Omnibus, The Cancer Genome Atlas pan-cancer tumors, and cell lines characterized by Sanger Genomics of Drug Sensitivity in Cancer to infer DNA damage response characteristics, genomic scar features, drug sensitivity, and radiation therapy outcomes. DSB repair capacity and pathway usage were validated using functional assays, including Alt-EJ reporters and droplet digital PCR quantification of microhomology-mediated repair events. Core Alt-EJ effectors such as PARP1 and POLQ were perturbed genetically and pharmacologically. Therapeutic efficacy of PARP or POLQ inhibition with or without irradiation was tested in a syngeneic OSCC model, followed by bulk tumor transcriptomics to assess pathway engagement. RESULTS: Upregulation of miR-21-5p was not only selectively detected in radioresistant OSCC, but also modulated radiosensitivity in vitro and in vivo, and was associated with inferior postradiation therapy survival. A calibrated miR-21-5p target-gene signature tracked Alt-EJ activity across patient and mouse tumors and cancer cell lines, correlated with microhomology-mediated indels and broader genomic scarring, and predicted sensitivity to clinically available PARP inhibitors. Functionally, enforced miR-21-5p expression increased Alt-EJ usage and accelerated DSB repair, whereas inhibition or depletion of key Alt-EJ effectors reduced repair efficiency and restored radiosensitivity. In vivo, Alt-EJ targeting with PARP or POLQ inhibitor abrogated miR-21-5p-driven radiation resistance; transcriptomic profiling supported suppression of Alt-EJ programs as the operative mechanism. CONCLUSIONS: These findings establish a mechanistic link between miR-21-5p activity and Alt-EJ dependence, provide a clinically deployable signature to identify Alt-EJ-dependent OSCC, and support rational combinations of Alt-EJ targeting agents with radiation therapy to overcome treatment failure and advance precision radiation oncology.

MicroRNAs↗

PubMed2026

Effect of protective ventilation throughout the intubation period on perioperative oxygenation in patients undergoing MIDCABG: a randomised controlled trial.

INTRODUCTION: Minimally invasive direct coronary artery bypass grafting (MIDCABG) requires prolonged one-lung ventilation (OLV), increasing postoperative pulmonary complications (PPCs) risk. We investigated whether protective lung ventilation (PLV) throughout intubation benefits MIDCABG patients. METHODS: In this single-center randomized study, MIDCABG patients received PLV (low tidal volume of 6-8 mL·kg-1, PEEP of 6 cm H2O, alveolar recruitment maneuvers) or conventional mechanical ventilation (CMV, tidal volume of 8-10 mL·kg-1, without PEEP or maneuvers) from tracheal intubation to extubation. The primary outcome was perioperative oxygenation, assessed by the PaO2/FiO2 ratio. RESULTS: Sixty patients (n = 30 per group) were enrolled. Compared with CMV, PLV improved PaO2/FiO2 ratios (mean difference at OLV60: 34.56 mmHg; 95% CI: 11.78-57.33; p < 0.01), shortened median durations of postoperative mechanical ventilation (median difference: -4.5 h, 95% CI: -8.5 to -0.5; p = 0.013) and hospital stay (median difference: -3.0 days, 95% CI: -5.0 to -1.0; p = 0.019). PLV also reduced driving pressure, airway pressure and intrapulmonary shunt during OLV (all p < 0.05). Desaturation occurred in 23.3% of CMV patients and 13.3% of PLV patients (p = 0.506). Hemodynamic parameters were generally comparable between groups, except for lower MPAP and PVRI in the PLV group during OLV and after ICU admission (p < 0.05). The incidence of PPCs did not differ between groups. CONCLUSIONS: In patients undergoing MIDCABG, PLV applied throughout intubation improved perioperative oxygenation and shortened the duration of postoperative mechanical ventilation and hospital stay, but did not reduce PPCs. CLINICAL TRIAL REGISTRATION: ChiCTR1900022005.

Humans↗

PubMed2026

Insights into the regulation of the HOTAIR proximal promoter.

HOTAIR (HOX transcript antisense RNA) is a HOXC-cluster long intervening non-coding RNA (lincRNA) whose cancer relevance is tightly coupled to how its transcription is wired into hormone, hypoxia, inflammatory, and developmental signaling. HOTAIR is known to associate with cancer cell proliferation, motility, tumor invasion, and metastasis. The present mini-review focuses on the regulatory architecture and mechanistic complexity of HOTAIR transcriptional regulation, with emphasis on three organizing principles. First, we consider the impact of promoter choice between a canonical proximal promoter (P1), which supports the 2.2-2.4 kb transcript, and an alternative upstream promoter/TSS (P2), which contributes to context-dependent transcription initiation. Second, we examine the long-distance enhancer-promoter communication between HOTAIR distal enhancer and P1/P2. Third, we summarize the recent epigenetic and epi-transcriptomic mechanisms involved in HOTAIR transcript initiation and elongation. A combination of these events determines isoform-specific transcription to govern cell-type-, context-, and cancer specific modulation of HOTAIR expression that promotes tumor formation and cancer progression. Finally, the review proposes how large-scale RNA datasets, long-read sequencing, and isoform-specific studies can refine our understanding of this versatile lincRNA's regulation.

Humans↗

PubMed2025

The molecular mechanism of cuproptosis and research progress in pancreatic diseases.

PURPOSE: Cuproptosis has been proven to be a novel mode of cell death, distinct from other types of cell death such as necrosis, ferroptosis, pyroptosis, and apoptosis. This study aims to systematically review the molecular mechanisms of cuproptosis in recent years and its research progress in pancreatic diseases. METHODS: By searching PubMed and Web of Science databases, 113 key literatures were included for thematic analysis, covering the molecular mechanism of cuproptosis and its role in the occurrence and development of pancreatic cancer, acute and chronic pancreatitis, diabetes, pancreatic cyst, pancreatic injury and pancreatic neuroendocrine tumor. RESULTS: Cuproptosis refers to the accumulation of copper ions in cells, which leads to instability of ferritin and aggregation of acylated proteins, resulting in oxidative stress-related cell death. Recent studies have shown that cuproptosis plays an important role in the occurrence and development of various pancreatic diseases, such as pancreatic cancer, acute and chronic pancreatitis, diabetes, pancreatic cysts, pancreatic injuries and pancreatic neuroendocrine tumor. The inducers of cuproptosis, such as disulfiram, chloroquinolones, and perilla phenols, alleviate pancreatic cancer by promoting cell cuproptosis. Copper chelators such as tetraethylenepentamine and tetrathiomolybdate promote the recovery of pancreatic injury by inhibiting cell cuproptosis. CONCLUSIONS: Cuproptosis plays a crucial role in the pathogenesis of pancreatic diseases. Further research on the cuproptosis pathway may become a potential target for the treatment of pancreatic diseases.

Animals↗

PubMed2026

Effect of transcutaneous auricular vagus nerve stimulation on postoperative pain in patients undergoing thoracoscopic partial lung resection: a randomized, double-blind, controlled clinical trial.

BACKGROUND: Postoperative pain after thoracic surgery remains common and challenging. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation technique with potential analgesic effects. This study aimed to evaluate the efficacy and safety of taVNS for postoperative pain management in patients undergoing thoracoscopic partial lung resection. METHODS: Adults undergoing thoracoscopic partial lung resection were randomized to active or sham taVNS. The primary outcome was cough pain intensity at 48h post-surgery, assessed by Numeric Rating Scale (NRS). Secondary outcomes included cough pain at 24h and 72h, resting pain, moderate-to-severe pain incidence, opioid consumption, quality of recovery, postoperative pulmonary complications , chest tube duration, hospital stay, postoperative nausea/vomiting, and adverse events. RESULTS: Among 119 analyzed patients (active n = 60, sham n = 59), active taVNS reduced cough pain scores at 24h, 48h, and 72h postoperatively, as well as resting pain (p < 0.05). It also lowered the incidence of moderate-to-severe cough pain at 24h and 48h, reduced cumulative postoperative opioid use at 24h and 72h, and decreased rescue analgesia on postoperative day 3 (p < 0.05). Active taVNS was associated with a lower incidence of postoperative pneumothorax (p < 0.05). No serious adverse events occurred. CONCLUSION: Perioperative taVNS was associated with a modest analgesic benefit and reduced postoperative opioid requirements after thoracoscopic partial lung resection. The observed reduction in postoperative pneumothorax requires cautious interpretation, and further multicenter trials are needed to determine its clinical utility.

Humans↗

PubMed2026

Targeted sequencing reveals a distinct genetic alteration landscape in oral multiple primary squamous cell carcinomas.

OBJECTIVE: Oral multiple primary cancers (MPCs) are associated with poor clinical outcomes, yet their genomic characteristics remain insufficiently understood. DESIGN: Fifty-four formalin-fixed paraffin-embedded (FFPE) tumor samples from 30 patients with oral MPCs were analyzed using high-depth targeted sequencing of a customized 14-gene panel derived from prior whole-exome sequencing data. Detected alterations were analyzed after removal of synonymous mutations. RESULTS: Non-silent genomic alterations were identified in 59.3% (32/54) of samples, involving 19 patients. A total of 70 variant loci across 13 genes were detected. AKAP13 was the most frequently mutated gene at both the sample (22.2%, 12/54), with recurrent mutations observed across multiple patients. In contrast, TP53 mutations occurred at a substantially lower frequency (11.1%, 6/54). Marked inter- and intra-patient mutational heterogeneity was observed. CONCLUSIONS: FFPE-based targeted sequencing enabled an initial characterization of genomic alterations in oral MPCs. Recurrent alterations in AKAP13, GLI2, JMJD1C, and DNAH8, together with the relatively low frequency of TP53 alterations, identify candidate genomic features for further investigation and provide a basis for future studies of the molecular basis of oral MPCs.

Humans↗

PubMed2026

The identification of growth-promoting lncRNAs in oral cavity squamous cell carcinoma.

Oral Cavity Squamous Cell Carcinoma (OCSCC) is an aggressive tumor that develops within the mouth of patients. Tumor-suppressor gene loss and genomic arrangements fuel tumorigenesis and transcriptional reprogramming. Understanding how these alterations contribute to OCSCC growth and cell survival may identify new therapeutic vulnerabilities or biomarkers. We profiled the role of long non-coding RNAs (lncRNAs) in the growth of three OCSCC cell lines using a CRISPRi-screen and identified 19 lncRNAs that contribute to OCSCC proliferation. By comparing these lncRNAs to other screens, we find that these lncRNAs are uniquely required in OCSCC and not other malignancies. We show that these lncRNAs are abundantly expressed in OCSCC cells and tumors. Independent testing of candidate lncRNAs confirms their role in supporting OCSCC growth. Our results show that a novel subset of lncRNAs are required for the growth of OCSCC cancer cells and that these lncRNAs are cell lineage specific.

CRISPRi↗

PubMed2026

Engineering bubble structures as Cas12a activators for highly sensitive monitoring of WRN helicase function.

The Werner syndrome helicase (WRN) is a critical synthetic lethal target in microsatellite instability cancers, essential for resolving complex genomic structures like replication bubbles and R-loops. However, strategies to simultaneously discriminate WRN activity on DNA versus DNA-RNA substrates in living cells are lacking. Here, we developed a structure-specific CRISPR/Cas12a biosensing strategy to visualize WRN functional activity by engineering bubble-structure probes. These probes were rationally designed to structurally mimic DNA replication bubbles and R-loop associated DNA-RNA hybrids. Upon specific unwinding by WRN, the probes release a sequestered activator strand that triggers Cas12a trans-cleavage, effectively converting the unwinding event into an amplified fluorescent signal. This assay achieves low picomolar sensitivity (LODs: 5.6-6.0 pM) and exceptional selectivity against homologous RecQ helicases. Uniquely, this strategy enables the parallel quantification of WRN activity on both substrate types, providing insights into distinct WRN-mediated pathways for resolving genomic stress. We further demonstrated the strategy's utility by visualizing endogenous WRN dynamics in living cells and profiling the efficacy of small-molecule inhibitors. This work offers a powerful molecular toolkit for dissecting WRN biology and facilitating high-throughput drug screening in targeted cancer therapy.

Werner Syndrome Helicase↗

PubMed2026

Robust optimisation for photon radiotherapy: A scoping review of models, paradigms, and reporting.

BACKGROUND AND PURPOSE: Robust optimisation offers an alternative to conventional margin-based photon radiotherapy planning by explicitly modelling uncertainty, but practice is variable and not standardised. MATERIALS AND METHODS: A scoping review was conducted to map robust optimisation for photon external beam radiotherapy. Electronic searches of Scopus, PubMed and Google Scholar (2000-2025, English language) identified planning studies that incorporated modelled uncertainties into the optimisation process and reported at least one robustness-related outcome. Data were charted on clinical context, uncertainty models, optimisation paradigms, robustness metrics and evidence for clinical implementation. RESULTS: Seventy-one studies were included. Most investigated prostate, breast or lung cancer and used intensity-modulated radiotherapy or volumetric-modulated arc therapy in commercial or research treatment planning systems. Scenario-based worst-case (minimax) optimisation was the dominant paradigm in clinically oriented work, while chance-constrained, conditional value at-risk, distributionally robust and adaptive formulations were confined to small methodological series. Uncertainty modelling focused mainly on rigid set-up error; fewer studies incorporated respiratory motion, inter-fraction anatomical change, dose-calculation uncertainty or biological variation. Robustness was evaluated with diverse scenario-based dose-volume metrics, probabilistic coverage measures, composite robustness indices and, less often, biological endpoints. Direct clinical implementation reports were scarce. CONCLUSION: Robust photon planning is technically feasible and generally maintains or improves target coverage and organ sparing compared with margin-based planning. However, heterogeneity in uncertainty models, optimisation configuration and robustness reporting limits comparison and synthesis. Pragmatic minimum standards are proposed to support future consensus and wider clinical adoption.

Humans↗