Farnesoid X receptor inhibits proliferation of human colorectal cancer cells via the miR‑135A1/CCNG2 signaling pathway

Qiao,Pengfei; Li,Shenglong; Zhang,Haogang; Yao,Lei; Wang,Fujing

doi:10.3892/or.2018.6636

Farnesoid X receptor inhibits proliferation of human colorectal cancer cells via the miR‑135A1/CCNG2 signaling pathway

Authors:
- Pengfei Qiao
- Shenglong Li
- Haogang Zhang
- Lei Yao
- Fujing Wang
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Affiliations: Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
Published online on: August 7, 2018 https://doi.org/10.3892/or.2018.6636
Pages: 2067-2078

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Abstract

Colorectal cancer (CRC) is among the most common malignancies of the digestive system. Dysregulation of miRNAs and the farnesoid X receptor (FXR) are involved in the progression of CRC. In the present study, the effects of FXR and miR‑135A1 in CRC were evaluated. Reverse transcription quantitative‑polymerase chain reaction (RT‑qPCR) was used to examine the expression of miR‑135A1 in patient CRC tissues and adjacent non‑tumor tissues, as well as cell lines. The association between miR‑135A1 and clinical characteristics of patients with CRC was also investigated. RT‑qPCR and western blotting were used to evaluate the expression of miR‑135A1 targets. Regulation of cyclin G2 (CCNG2) by miR‑135A1was confirmed using luciferase assays. The biological effects of miR‑135A1 were assessed in transfected and untransfected CRC cell lines using colony formation assays, cell‑cycle analysis by flow cytometry, and CCK‑8 assays. miR‑135A1 was upregulated in CRC specimens and cell lines. miR‑135A1 expression was strongly associated with poor cell differentiation, high expression of carbohydrate antigen (CA)125, CA199, carcinoembryonic antigen and survival rate of patients with CRC. Expression of CCNG2 was downregulated in CRC patients and cell lines, and was further demonstrated to be among the downstream targets of miR‑135A1. The present study indicated that inhibition of miR‑135A1 expression leads to cell cycle arrest and inhibition of proliferation of CRC cells via increasing CCNG2 expression. In the present study, activation of FXR by GW4064 increased CCNG2 expression via suppression of miR‑135A1 expression, and the FXR/miR‑135A1/CCNG2 axis was demonstrated to be involved in mediating cell proliferation. In conclusion, activation of FXR by GW4064 suppresses cell proliferation and causes cell cycle arrest in CRC, and the miR‑135A1/CCNG2 pathway was suggested to be involved in this step.

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