Combinatorial Chemistry & High Throughput ScreeningCombinatorial Chemistry & High Throughput ScreeningCombinatorial Chemistry & High Throughput Screening1386-20731875-5402Bentham Science64399310.2174/0113862073267943231101065948ChemistryResearch ArticleKnockdown of LRCH4 Remodels Tumor Microenvironment Through Inhibiting YAP and TGF-β/Smad Signaling Pathway in Colorectal CancerLiZhiweninfo@benthamscience.netCuiZhenhuainfo@benthamscience.netWangXianreninfo@benthamscience.netLvYanfenginfo@benthamscience.netThe Second Hospital, Cheeloo College of Medicine, Shandong University,The Second Hospital, Cheeloo College of Medicine, Shandong University1506202427121823182907012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://rjpbr.com/1386-2073/article/view/643993

Background::Colorectal cancer is one of the most common gastrointestinal malignancies worldwide. LRCH4 is the top 1 gene associated with an unfavorable prognosis in colorectal cancer.

Methods::Here, we reported that the knockdown of LRCH4 inhibited the proliferation, migration and invasion in HT29 cells.

Results::The activity of Yes-Associated Protein (YAP), a transcription factor in the Hppo-YAP signaling pathway, was significantly inhibited by LRCH4-siRNA. LRCH4 knockdown also reversed the EMT and regulated the expression of extracellular matrix (ECM) protein, Fibronectin and Collagen IV in HT29 cells. In addition, the TGF-β/Smad signaling pathway, as the downstream pathway of Yap, was also inhibited by LRCH4 knockdown.

Conclusion::Knockdown of LRCH4 involved in the regulation of ECM and EMT and inhibited YAP and the TGF-β/Smad signaling pathway in colorectal cancer cells. Our study provided a mechanism of LRCH4 on colorectal cancer cells, and a new potential target for clinical tumor treatment

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