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LncRNA SNHG7 通过海绵吸附 miR-216b 促进结直肠癌细胞的增殖和肝转移,上调 GALNT1 表达。

LncRNA SNHG7 sponges miR-216b to promote proliferation and liver metastasis of colorectal cancer through upregulating GALNT1.

机构信息

College of Laboratory Medicine, Dalian Medical University, 116044, Dalian, Liaoning Province, China.

出版信息

Cell Death Dis. 2018 Jun 18;9(7):722. doi: 10.1038/s41419-018-0759-7.

Abstract

Accumulating evidence suggests long noncoding RNAs (lncRNAs) play an important role in cancer progression. However, the function of lncRNA SNHG7 in colorectal cancer (CRC) remains unclear. In this study, SNHG7 expression was significantly upregulated in CRC tissues, especially in aggressive cases. In accordance, high level of SNHG7 was observed in CRC cell lines compared to normal colon cells. Furthermore, SNHG7 overexpression promoted the proliferation, migration, and invasion of CRC cell lines, while SNHG7 depletion inhibited invasion and cell viability in vitro. Mechanistically, knockdown of SNHG7 inhibited GALNT1 and EMT markers (E-cadherin and Vimentin). Importantly, SNHG7 directly interacted with miR-216b and downregulation of miR-216b reversed efficiently the suppression of GALNT1 induced by SNHG7 siRNA. Moreover, overexpression of SNHG7 significantly enhanced the tumorigenesis and liver metastasis of SW480 cells in vivo. SNHG7 positively regulated GALNT1 level through sponging miR-216b, and played an oncogenic role in CRC progression. Together, our study elucidated the role of SNHG7 as an miRNA sponge in CRC, and shed new light on lncRNA-directed diagnostics and therapeutics in CRC.

摘要

越来越多的证据表明,长非编码 RNA(lncRNA)在癌症进展中发挥重要作用。然而,lncRNA SNHG7 在结直肠癌(CRC)中的作用尚不清楚。在本研究中,SNHG7 在 CRC 组织中表达显著上调,尤其是在侵袭性病例中。相应地,与正常结肠细胞相比,CRC 细胞系中 SNHG7 的水平较高。此外,SNHG7 过表达促进 CRC 细胞系的增殖、迁移和侵袭,而 SNHG7 耗竭则抑制体外侵袭和细胞活力。机制上,SNHG7 的敲低抑制了 GALNT1 和 EMT 标志物(E-钙黏蛋白和波形蛋白)。重要的是,SNHG7 可直接与 miR-216b 相互作用,下调 miR-216b 可有效逆转 SNHG7 siRNA 对 GALNT1 的抑制作用。此外,SNHG7 的过表达显著增强了 SW480 细胞在体内的致瘤性和肝转移。SNHG7 通过海绵吸附 miR-216b 正向调节 GALNT1 水平,在 CRC 进展中发挥致癌作用。总之,我们的研究阐明了 SNHG7 在 CRC 中作为 miRNA 海绵的作用,并为 CRC 的 lncRNA 导向诊断和治疗提供了新的思路。

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