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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

Knockdown of LRCH4 Remodels Tumor Microenvironment Through Inhibiting YAP and TGF-β/Smad Signaling Pathway in Colorectal Cancer

Author(s): Zhiwen Li, Zhenhua Cui, Xianren Wang and Yanfeng Lv*

Volume 27, Issue 12, 2024

Published on: 20 November, 2023

Page: [1823 - 1829] Pages: 7

DOI: 10.2174/0113862073267943231101065948

Price: $65

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Abstract

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.

Keywords: Colorectal cancer, prognosis, tumor microenvironment, YAP, epithelial mesenchymal transformation, calponin homology (CH).

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