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miR-137 抑制肾透明细胞癌的肿瘤生长和转移。

MiR-137 suppresses tumor growth and metastasis in clear cell renal cell carcinoma.

机构信息

Department of Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.

Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, China.

出版信息

Pharmacol Rep. 2018 Oct;70(5):963-971. doi: 10.1016/j.pharep.2018.04.006. Epub 2018 Apr 22.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

MiR-137 serves as a tumor suppressor, which can be considered a potential therapeutic target in ccRCC.

摘要

背景

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。

方法

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。

结果

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。

结论

miR-137 作为肿瘤抑制因子,可被视为 ccRCC 的潜在治疗靶点。

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