TRPM7 deficiency suppresses cell proliferation, migration, and invasion in human colorectal cancer via regulation of epithelial-mesenchymal transition

Article type: Research Article

Authors: Su, Fei^a | Wang, Bo-Fang^b | Zhang, Tao^{a; b} | Hou, Xiao-Ming^{a; *} | Feng, Mao-Hui^{c; d; e; f; *}

Affiliations: [a] Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China | [b] The Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China | [c] Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China | [d] Clinical Cancer Study Center of Hubei Provence, Wuhan, Hubei, China | [e] Key Laboratory of Tumor Biological Behavior of Hubei Provence, Wuhan, Hubei, China | [f] Center for Clinical Medicine of Peritoneal Cancer of Wuhan, Wuhan, Hubei, China

Correspondence: [*] Corresponding authors: %****␣cbm-26-cbm190666_temp.tex␣Line␣25␣**** Xiao-Ming Hou, The First Hospital of Lanzhou University, Donggang West Road, Chengguan District, Lanzhou, Gansu 730000, China. E-mail: [email protected]; Mao-Hui Feng, Zhongnan Hospital of Wuhan University, No. 169 of Donghu Road, Wuchang District, Wuhan, Hubei 430071, China. E-mail: [email protected].

Abstract: BACKGROUND: It has been documented that transient receptor potential melastatin 7 (TRPM7) plays a pivotal role in the development of multiple cancers. However, the role of TRPM7 in human colorectal cancer (CRC) is poorly understood. Therefore, the aim of this study was to investigate the expression and significance of TRPM7 in CRC. METHODS: In this study, TRPM7 expression was first investigated in Gene Expression Omnibus (GEO), and then validated it with the data from our medical center. CCK-8, colony survival, transwell, and flow cytometry assays were employed to evaluate the effects of TRPM7 knockdown on the CRC cell proliferation, migration, and invasion, as well as cell cycle and apoptosis. RESULTS: We observed markedly increased TRPM7 expression in CRC tissues. CRC patients with high expression of TRPM7 suggested deeper tumor infiltration, positive lymph node metastasis, distant metastasis, and advanced clinical stage. In addition, TRPM7 was also overexpressed in CRC cell lines. Downregulated TRPM7 in vitro suppressed CRC cell proliferation, migration, and invasion, as well as triggered cell cycle arrest at the G0/G1 phase, reduced the S phase, and promoted apoptosis. Importantly, decreased TRPM7 in CRC cells reversed the epithelial-mesenchymal transition (EMT) status, accompanied by downregulation of N-cadherin and upregulation of E-cadherin. CONCLUSION: Our study indicated that the expression of TRPM7 was positively correlated with tumor infiltration, lymph node metastasis, distant metastasis and clinical stage of CRC. Besides, decreased TRPM7 in vitro inhibited CRC cell proliferation, migration and invasion by modulating EMT.

Keywords: TRPM7, colorectal cancer, proliferation, migration, invasion, epithelial-mesenchymal transition

DOI: 10.3233/CBM-190666

Journal: Cancer Biomarkers, vol. 26, no. 4, pp. 451-460, 2019