Transcription factor forkhead box K1 regulates miR‑32 expression and enhances cell proliferation in colorectal cancer

Wu,Weiyun; Chen,Yongze; Ye,Shicai; Yang,Hui; Yang,Jianyun; Quan,Juanhua

doi:10.3892/ol.2021.12668

Transcription factor forkhead box K1 regulates miR‑32 expression and enhances cell proliferation in colorectal cancer

Authors:
- Weiyun Wu
- Yongze Chen
- Shicai Ye
- Hui Yang
- Jianyun Yang
- Juanhua Quan
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Affiliations: Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
Published online on: March 22, 2021 https://doi.org/10.3892/ol.2021.12668
Article Number: 407
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Increased microRNA (miR)‑32 expression in colorectal cancer (CRC) tissues enhances CRC cell proliferation, migration, invasion and attenuates CRC cell apoptosis by repressing the expression of phosphatase and tensin homolog (PTEN). Forkhead box K1 (FOXK1) was identified as a potential interacting transcription factor using DNA pull‑down assays and mass spectrometry. The present study aimed to elucidate the role of FOXK1 in regulating miR‑32 expression in CRC. The expressions of FOXK1, miR‑32, transmembrane protein 245 gene (TMEM245) and PTEN were compared between CRC and normal colonic tissues. Levels of miR‑32, TMEM245, PTEN and the proliferation and apoptosis of CRC cells were studied using FOXK1‑overexpression or knockdown, or by simultaneously interfering with FOXK1 and miR‑32 expression. Direct FOXK1 binding to the miR‑32 promoter was verified using chromatin immunoprecipitation (ChIP) and dual‑luciferase reporter assays. The results showed elevated FOXK1, miR‑32 and TMEM245 expression, and significantly decreased PTEN expression in CRC, compared with normal colonic tissues. Correlations between the expressions of TMEM245 and miR‑32, FOXK1 and miR‑32, and FOXK1 and TMEM245 were positive and significant. FOXK1‑knockdown led to decreased miR‑32 and TMEM245 expression and increased PTEN expression, whereas FOXK1‑overexpression had the opposite effect. Overexpressed FOXK1 promoted the malignancy of CRC cells in vitro by stimulating proliferation and reducing apoptosis; whereas FOXK1‑depletion suppressed such malignancy and a miR‑32 inhibitor partially reversed the effects of FOXK1. The results of ChIP and dual‑luciferase reporter assays indicated that FOXK1 directly binds to the promoter of TMEM245/miR‑32. Thus, the FOXK1‑miR‑32‑PTEN signaling axis may play a crucial role in the pathogenesis and development of CRC.

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