Department of Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, China.
Pharmacol Rep. 2018 Oct;70(5):963-971. doi: 10.1016/j.pharep.2018.04.006. Epub 2018 Apr 22.
The most frequent type of renal cell carcinoma is called clear-cell renal cell carcinoma (ccRCC) which is associated with a poor prognosis. It has been observed that miR-137 is aberrantly expressed in many different kinds of human malignancies including ccRCC. This research aims to examine the role of miR-137 in ccRCC.
Quantitative RT-PCR (qRT-PCR) was applied to measure miR-137 expression in ccRCC and adjacent noncancerous tissue. Gene expression was determined by western blot. Cell Counting Kit-8 (CCK-8) assay, flow cytometry and Transwell assay were used to determine the effects of miR-137 on cell growth, apoptosis and invasion, respectively. Moreover, xenograft and pulmonary metastasis animal models were established to investigate the role of miR-137 in vivo.
Our findings show that there was significant downregulation of miR-137 in ccRCC tissue relative to corresponding non-cancerous tissue. Ectopic miR-137 expression in ccRCC cells led to suppression of cell growth and invasion, as well as apoptosis induction. In contrast, knockdown of miR-137 enhances proliferation and invasion, inhibits apoptosis. It also confirms that miR-137 plays a tumor supressor role in vivo. Mechanically, miR-137 directly targets the 3'-UTR of RLIP76 which is an established oncogene in ccRCC.
MiR-137 serves as a tumor suppressor, which can be considered a potential therapeutic target in ccRCC.
最常见的肾细胞癌类型称为透明细胞肾细胞癌(ccRCC),其预后不良。已经观察到 miR-137 在许多不同类型的人类恶性肿瘤中异常表达,包括 ccRCC。本研究旨在研究 miR-137 在 ccRCC 中的作用。
采用定量 RT-PCR(qRT-PCR)测量 ccRCC 和相邻非癌组织中的 miR-137 表达。通过 Western blot 确定基因表达。细胞计数试剂盒-8(CCK-8)测定、流式细胞术和 Transwell 测定分别用于确定 miR-137 对细胞生长、凋亡和侵袭的影响。此外,建立异种移植和肺转移动物模型以研究 miR-137 在体内的作用。
我们的研究结果表明,与相应的非癌组织相比,ccRCC 组织中 miR-137 的表达显著下调。ccRCC 细胞中 miR-137 的异位表达导致细胞生长和侵袭的抑制以及凋亡的诱导。相反,miR-137 的敲低增强了增殖和侵袭,抑制了凋亡。它还证实 miR-137 在体内发挥肿瘤抑制作用。从机制上讲,miR-137 直接靶向 RLIP76 的 3'-UTR,RLIP76 是 ccRCC 中的一种已建立的癌基因。
miR-137 作为肿瘤抑制因子,可被视为 ccRCC 的潜在治疗靶点。