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Results for “FMRP”

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4 recordsLinked to original sources
PubMed2026

FMRP promotes gastric cancer progression via m6A-dependent stabilization of DVL2 and activation of the Wnt/PCP-JNK pathway.

BACKGROUND: N6-methyladenosine (m6A) modification has emerged as a critical regulator in gastric cancer progression. Fragile X messenger ribonucleoprotein 1 (FMRP), an RNA-binding protein with tumorigenic potential, remains poorly characterized in gastric cancer. METHODS: FMRP expression in gastric cancer was assessed through bioinformatic analyses and tissue microarray-based immunohistochemistry. Its biological functions were examined through loss-of-function experiments in vitro and in vivo. Mechanistic investigations, including RNA interaction, m6A site mutation, and RNA stability analyses, were performed to identify downstream targets and pathways regulated by FMRP. RESULTS: Bioinformatic analyses and tissue microarray-based immunohistochemistry showed that FMRP was significantly upregulated in gastric cancer tissues. FMRP depletion suppressed tumor growth and metastasis. Subsequently, Dishevelled segment polarity protein 2 (DVL2) was identified as a candidate downstream target of FMRP. DVL2 was also significantly upregulated in gastric cancer tissues, and its expression positively correlated with FMRP expression. Mechanistically, FMRP bound to DVL2 mRNA and enhanced its stability in an m6A-dependent manner. Among the candidate sites tested, mutation of 1271A attenuated FMRP-mediated regulation of DVL2 reporter activity, supporting the involvement of this site. Functionally, FMRP promoted activation of the noncanonical Wnt/planar cell polarity (PCP) signaling pathway and enhanced the proliferative, migratory, and invasive capacities of gastric cancer cells via DVL2. CONCLUSIONS: These results define FMRP as an oncogenic driver in gastric cancer that operates via the DVL2/Wnt/PCP axis. Targeting this pathway may provide a potential therapeutic strategy for gastric cancer.

Stomach Neoplasms↗
PubMed1987

The adoption and implementation of the fluoride mouthrinse program: descriptive results from school districts.

Systematic research is needed about the dissemination and use of effective caries prevention measures to establish adoption trends and to examine factors related to desired practice. This paper examines the adoption and implementation of the fluoride mouthrinse program (FMRP) in public school districts. It extends a similar study by Silversin and Coombs in 1979 by reporting telephone interview data from the same sample of school districts. The results indicate that the extent of FMRP adoption has increased since 1979, but that the recent rate of new adopters has slowed considerably. About one-quarter of the districts that had ever offered the FMRP have since discontinued it, most frequently by gradual abandonment. The reported accuracy of school level implementation was assessed in terms of seven required components of the FMRP. Only 57 percent of the sample reported implementing six or seven components correctly, showing at best only moderate accuracy of delivery at the local level.

Attitude to Health↗
PubMed1988

The role of linking agents in the diffusion of health promotion programs.

This article examines the role of state health department dental offices as linking agents in the diffusion of an effective preventive health program, the fluoride mouthrinse program (FMRP) in public schools. The aim of this program is to prevent dental caries by a weekly mouthrinsing by elementary school students. In contrast to the traditional focus of diffusion research on characteristics of the innovation and characteristics of the adopter, this study emphasizes an ecological approach, i.e., the transmittal mechanisms for diffusion. The state dental offices are examined as linking agents, which serve as program advocates or champions for diffusing the FMRP from the national level, where it was developed, to the thousands of local school districts and schools for adoption and continued delivery. Using data from interviews with state dental directors and archival sources, a multivariate model was developed and used to explain the percent of a state's elementary schools using the mouthrinse program. The results support the key role of linking agents in disseminating effective health promotion programs into actual use. Implications are discussed for both research and practice.

Dental Caries↗
PubMed2026

Altered ECM deposition and cell adhesion signaling in a human cortical organoid model of fragile X syndrome.

Fragile X Syndrome (FXS) is the most common inherited intellectual disability, and the most common monogenic cause of autism spectrum disorder (ASD). It is caused by epigenetic silencing of the FMR1 gene leading to the loss of FMRP, an RNA-binding protein that regulates local mRNA translation in neuronal dendrites, crucial for synapse development. Three-dimensional (3D) brain organoid models derived through in vitro differentiation of pluripotent stem cells offer a powerful tool to dissect the underlying mechanisms of neurodevelopmental disorders. Here, we generated human FXS and control organoids using isogenic human embryonic stem cell clones with and without the FXS mutation. Our results show that mature FXS cortical brain organoids can be derived by inhibiting the TGFβ and Wnt pathways. Moreover, expression analyses including immunofluorescence, qRT-PCR, proteomics and western blotting reveal altered levels of neuronal markers and ECM deposition along with modulated downstream signaling molecules. Interestingly, in silico analysis of proteomics revealed several altered pathways, such as cell adhesion, regulation of neurogenesis and cell cycle that are implicated in FXS. Collectively, our unique FXS-organoids derived from isogenic hESC lines may serve as a model for studying the pathology of FXS disorder and for developing therapeutical intervention.

Humans↗