Mex-3 RNA Binding Family Member A Modulates Peroxisome Proliferator-Activated Receptor Gamma Pathway Activity and Colorectal Cancer Growth.
1/5 보강
[BACKGROUND & AIMS] RNA-binding proteins (RBPs) are major effectors of post-transcriptional regulation.
- 표본수 (n) 172
- p-value P = .039
APA
Silva AR, Coelho A, et al. (2026). Mex-3 RNA Binding Family Member A Modulates Peroxisome Proliferator-Activated Receptor Gamma Pathway Activity and Colorectal Cancer Growth.. Cellular and molecular gastroenterology and hepatology, 101771. https://doi.org/10.1016/j.jcmgh.2026.101771
MLA
Silva AR, et al.. "Mex-3 RNA Binding Family Member A Modulates Peroxisome Proliferator-Activated Receptor Gamma Pathway Activity and Colorectal Cancer Growth.." Cellular and molecular gastroenterology and hepatology, 2026, pp. 101771.
PMID
41881339 ↗
Abstract 한글 요약
[BACKGROUND & AIMS] RNA-binding proteins (RBPs) are major effectors of post-transcriptional regulation. Recently, we described the role of Mex-3 RNA binding family member A (MEX3A) in maintaining leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5)+ intestinal stem cells identity and epithelial renewal. This work aimed to study MEX3A functional impact in colorectal cancer (CRC).
[METHODS] We characterized MEX3A expression profile in CRC mouse models and a cohort of CRC cases (n = 172). Mouse CRC tissues were used for the establishment of tumoroids and CRISPR/Cas9-mediated MEX3A knockout was performed in patient-derived CRC tumoroids to further understand its biological and therapeutic relevance. Simultaneously, we implemented the high-throughput technique HyperTRIBE to uncover MEX3A RNA targets.
[RESULTS] Intestinal adenomas from Apc mice have increased Mex3a expression, and Apc;Mex3a animals presented a significant reduction in tumor burden. Apc;Kras;Mex3a compound mice exhibited reduced tumor area, whereas corresponding tumoroids had reduced growth ability and enhanced differentiation potential associated with increased peroxisome proliferator-activated receptor gamma (PPARγ) signaling. MEX3A overexpression was observed in 85% of human CRC cases, whereas 72% presented PPARγ downregulation, with a significant inverse correlation (P = .039). Accordingly, MEX3A-depleted patient-derived CRC tumoroids showed decreased LGR5 expression, accompanied by increased PPARγ expression and higher sensitivity to 5-fluorouracil/oxaliplatin (FOLFOX)-based chemotherapy. HyperTRIBE results revealed a direct interaction between MEX3A and PPARG transcripts.
[CONCLUSIONS] MEX3A contributes to colorectal carcinogenesis, in association with PPARγ signaling modulation, impacting tumor development and therapeutic response.
[METHODS] We characterized MEX3A expression profile in CRC mouse models and a cohort of CRC cases (n = 172). Mouse CRC tissues were used for the establishment of tumoroids and CRISPR/Cas9-mediated MEX3A knockout was performed in patient-derived CRC tumoroids to further understand its biological and therapeutic relevance. Simultaneously, we implemented the high-throughput technique HyperTRIBE to uncover MEX3A RNA targets.
[RESULTS] Intestinal adenomas from Apc mice have increased Mex3a expression, and Apc;Mex3a animals presented a significant reduction in tumor burden. Apc;Kras;Mex3a compound mice exhibited reduced tumor area, whereas corresponding tumoroids had reduced growth ability and enhanced differentiation potential associated with increased peroxisome proliferator-activated receptor gamma (PPARγ) signaling. MEX3A overexpression was observed in 85% of human CRC cases, whereas 72% presented PPARγ downregulation, with a significant inverse correlation (P = .039). Accordingly, MEX3A-depleted patient-derived CRC tumoroids showed decreased LGR5 expression, accompanied by increased PPARγ expression and higher sensitivity to 5-fluorouracil/oxaliplatin (FOLFOX)-based chemotherapy. HyperTRIBE results revealed a direct interaction between MEX3A and PPARG transcripts.
[CONCLUSIONS] MEX3A contributes to colorectal carcinogenesis, in association with PPARγ signaling modulation, impacting tumor development and therapeutic response.