MiR-337-3p suppresses the proliferation and metastasis of clear cell renal cell carcinoma cells via modulating Capn4

Article type: Research Article

Authors: Zhuang, Qianfeng^{a; 1} | Shen, Jie^{a; 1} | Chen, Zhen^{a; 1} | Zhang, Mingran^a | Fan, Min^a | Xue, Dong^a | Lu, Hao^a | Xu, Renfang^a | He, Xiaozhou^{a; *} | Hou, Jianquan^{b; *}

Affiliations: [a] Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China | [b] Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

Correspondence: [*] Corresponding authors: Xiaozhou He, Department of Urology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou 213003, Jiangsu, China. Tel.: +86 18136392428; E-mail: czyyhxz@163.com.JianquanHou,DepartmentofUrology,TheFirstAffiliatedHospitalofSoochowUniversity,899PinghaiRoad,Suzhou215006,Jiangsu,China.Tel.:+8613813586637;E-mail:charleszhuang@me.com.

Note: [1] Authors equally contributed to this work.

Abstract: OBJECTIVE: Renal cancer accounts for about 3% of human cancer, and clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. Recently, microRNAs (miRNAs) are found to be the biomarkers for cancer diagnosis, prognosis and the targets for tumor management. This study aimed to examine the expression of miR-337-3p in ccRCC and to elucidate the molecular mechanisms underlying miR-337-3p-mediated ccRCC progression. METHODS: The miRNA and mRNA expression levels in ccRCC cells and tissues were measured by qRT-PCR. Cell proliferation, cell adhesion, colony growth and cell invasion were examined by CCK-8 assay, cell adhesion assay, colony formation assay and Transwell invasion assay, respectively. The protein levels were detected by western blot assay. The effects of miR-337-3p on tumor growth in vivo was assessed in a nude mice xenograft model. RESULTS: MiR-337-3p was down-regulated in ccRCC cell lines, and miR-337-3p overexpression suppressed cell proliferation, colony growth and invasion, but enhanced cell adhesion in ccRCC; while knockdown of miR-337-3p exerted the opposite effects on ccRCC. Bioinformatics analysis and luciferase reporter assay showed that Calpain small subunit 1 (Capn4) was negatively regulated by miR-337-3p, and overexpression of miR-337-3p attenuated the miR-337-3p-mediated effects on ccRCC cellular functions. In addition, miR-337-3p also suppressed epithelial-mesenchymal transition in ccRCC. The in vivo tumor growth was markedly suppressed after miR-337-3p overexpression. Data from clinical data showed that down-regulation of miR-337-3p and up-regulation of Capn4 mRNA and protein were identified in the ccRCC tissues, and miR-337-3p expression level was inversely correlated with Capn4 mRNA expression level in ccRCC tissues. CONCLUSIONS: Collectively, these data suggested the tumor suppressive role of miR-337-3p in ccRCC. MiR-337-3p suppressed cell proliferation and metastasis in ccRCC partially via targeting Capn4.

Keywords: ccRCC, miR-337-3p, Capn4, epithelial-mesenchymal transition, proliferation, metastasis

DOI: 10.3233/CBM-181645

Journal: Cancer Biomarkers, vol. 23, no. 4, pp. 515-525, 2018