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

LncRNA SNHG7 sponges miR-216b to promote proliferation and liver metastasis of colorectal cancer through upregulating GALNT1.
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DOI:
10.1038/s41419-018-0759-7
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发表时间:
2018-06-18
影响因子:
9
通讯作者:
Jia L
Jia L
中科院分区:
生物学1区
文献类型:
--
作者:
Shan Y;Ma J;Pan Y;Hu J;Liu B;Jia L

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越来越多的证据表明,长非编码RNA(LncRNAs)在癌症进展中发挥着重要作用。然而,LncRNA SNHG7在结直肠癌(CRC)中的功能仍不清楚。在本研究中,SNHG7在结直肠癌组织中的表达显著上调,尤其是在侵袭性病例中。相应地,与正常结肠细胞相比,结直肠癌细胞株中SNHG7的表达水平较高。此外,SNHG7过表达促进了结直肠癌细胞的增殖、迁移和侵袭,而SNHG7缺失则抑制了体外侵袭和细胞活力。在机制上,SNHG7的敲除抑制了GALNT1和EMT标记物(E-钙粘蛋白和Vimentin)。重要的是,SNHG7与miR-216B直接相互作用,miR-216B的下调有效地逆转了SNHG7 siRNA对GALNT1的抑制作用。此外,SNHG7的过表达显著增强了SW480细胞的体内成瘤和肝转移。SNHG7通过海绵miR-216B正向调节GALNT1水平,在结直肠癌发生发展中发挥致癌作用。总之,我们的研究阐明了SNHG7在结直肠癌中作为miRNA海绵的作用,并为lncRNA指导的结直肠癌诊断和治疗提供了新的线索。
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.
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