J Cancer 2021; 12(17):5345-5354. doi:10.7150/jca.60543

Research Paper

FHL1 Inhibits the Progression of Colorectal Cancer by Regulating the Wnt/β-Catenin Signaling Pathway

Yujing Liu1*, Chunyan Wang1*, Peiqiu Cheng1, Shengan Zhang2, Wenjun Zhou1, Yangxian Xu3, Hanchen Xu1✉, Guang Ji1✉

1. Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
2. Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
3. Department of General Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
*These authors contributed equally to this work.

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Citation:
Liu Y, Wang C, Cheng P, Zhang S, Zhou W, Xu Y, Xu H, Ji G. FHL1 Inhibits the Progression of Colorectal Cancer by Regulating the Wnt/β-Catenin Signaling Pathway. J Cancer 2021; 12(17):5345-5354. doi:10.7150/jca.60543. Available from https://www.jcancer.org/v12p5345.htm

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Abstract

Purpose: This study aims to explore the FHL1 expression level in colorectal cancer (CRC) patients, analyze its association with patient survival and investigate the role of FHL1 in CRC.

Methods: We used secondary sequencing to profile mRNA expression in CRC tissue and corresponding adjacent normal tissue from four CRC patients. We focus on FHL1 and analyzed the association between its expression level and clinical indicators. Furthermore, we explored the functional role of FHL1 in colorectal cancer tumorigenesis by transfecting cells with siRNA or overexpression plasmids.

Results: Hierarchical clustering revealed significantly differentially expressed mRNAs. FHL1 expression was significantly lower in CRC tissue than in adjacent normal tissue as well as in CRC cell lines relative to NCM460. Low FHL1 expression in CRC tissue correlated with poor patient survival. Our data demonstrated that overexpression of FHL1 inhibited the proliferation, colony formation potential, and expression of CdK4 and Cyclin D1, whereas ablating FHL1 promoted their proliferation and colony formation potential, suggesting that FHL1 acts as a tumor suppressor in CRC. Moreover, we showed that FHL1 inhibited the proliferation of colorectal cancer cells by negatively regulating the Wnt/β-catenin signaling pathway.

Conclusion: FHL1 is a potential tumor suppressor gene in colorectal cancer, and regulation of the FHL1-Wnt/β-catenin pathway may be part of its antitumor mechanism.

Keywords: Colorectal cancer, FHL1, RNA sequencing, Wnt/β-catenin signaling pathway