miR-337-3p 通过调节 Capn4 抑制透明细胞肾细胞癌细胞的增殖和转移。
MiR-337-3p suppresses the proliferation and metastasis of clear cell renal cell carcinoma cells via modulating Capn4.
机构信息
Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
出版信息
Cancer Biomark. 2018;23(4):515-525. doi: 10.3233/CBM-181645.
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.
目的
肾癌约占人类癌症的 3%，其中透明细胞肾细胞癌（ccRCC）是最常见的肾癌亚型。最近，microRNAs（miRNAs）被发现是癌症诊断、预后的生物标志物，也是肿瘤管理的靶点。本研究旨在检测 miR-337-3p 在 ccRCC 中的表达，并阐明 miR-337-3p 介导的 ccRCC 进展的分子机制。
方法
通过 qRT-PCR 检测 ccRCC 细胞和组织中的 miRNA 和 mRNA 表达水平。通过 CCK-8 测定、细胞黏附测定、集落生长测定和 Transwell 侵袭测定分别检测细胞增殖、细胞黏附、集落生长和细胞侵袭。通过 Western blot 测定检测蛋白水平。在裸鼠异种移植模型中评估 miR-337-3p 对肿瘤生长的影响。
结果
miR-337-3p 在 ccRCC 细胞系中下调，miR-337-3p 过表达抑制 ccRCC 中的细胞增殖、集落生长和侵袭，但增强细胞黏附；而 miR-337-3p 的敲低则对 ccRCC 产生相反的影响。生物信息学分析和荧光素酶报告基因测定表明，钙蛋白酶小亚基 1（Capn4）受 miR-337-3p 负调控，过表达 miR-337-3p 减弱了 miR-337-3p 对 ccRCC 细胞功能的调节作用。此外，miR-337-3p 还抑制了 ccRCC 中的上皮-间充质转化。过表达 miR-337-3p 后，体内肿瘤生长明显受到抑制。临床数据分析显示，在 ccRCC 组织中，miR-337-3p 下调，Capn4mRNA 和蛋白上调，并且在 ccRCC 组织中，miR-337-3p 的表达水平与 Capn4mRNA 的表达水平呈负相关。
结论
综上所述，这些数据表明 miR-337-3p 在 ccRCC 中具有肿瘤抑制作用。miR-337-3p 通过靶向 Capn4 部分抑制 ccRCC 中的细胞增殖和转移。
Zotero 插件