Small nucleolar RNA host gene 1 promotes development and progression of colorectal cancer through negative regulation of miR-137
Small nucleolar RNA host gene 1 promotes development and progression of colorectal cancer through negative regulation of miR-137
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小核仁RNA宿主基因1通过miR-137的负调控促进结直肠癌的发生和进展
DOI：
10.1002/mc.23101
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发表时间：
2019-08-30
影响因子：
4.6
通讯作者：
Qin, Yiyu
中科院分区：
文献类型：
--
作者：
Fu, Yang;Yin, Yuhan;Qin, Yiyu
小核仁RNA宿主基因1 （SNHG1）在癌症的进展中起关键作用。然而，SNHG1调控结直肠癌（CRC）进展的机制尚不清楚。采用实时定量聚合酶链反应检测CRC组织和细胞系中SNHG1和miR-137的表达。通过荧光素酶报告基因检测来研究miR-137的靶点。此外，通过RNA下拉实验探索miR-137、SNHG1和RNA诱导沉默复合体（RISC）之间的物理关联。流式细胞术（FCM）和transwell法检测细胞周期和侵袭。采用小鼠异种移植模型检测SNHG1的体内致癌活性。Western blot检测RICTOR、丝氨酸/苏氨酸激酶1 （AKT）、血清和糖皮质激素诱导激酶1 （SGK1）、p70S6K1和LC3II/LC3I比值的表达。SNHG1在结直肠癌组织和细胞系中表达上调，与淋巴结转移、TNM分期晚期、预后较差有关。SNHG1通过海绵miR-137增加CRC中的RICTOR水平。此外，SNHG1沉默在体外和体内均能抑制结直肠癌细胞的增殖和迁移。SNHG1通过海绵化miR-137调控RICTOR表达，促进结直肠癌的肿瘤发生。
Small nucleolar RNA host gene 1 (SNHG1) is critical in the progression of cancers. However, the mechanism by which SNHG1 regulates the progression of colorectal cancer (CRC) remains unclear. Expressions of SNHG1 and miR-137 in CRC tissues and cell lines were evaluated by quantitative real-time polymerase chain reaction. A luciferase reporter gene assay was conducted to investigate miR-137 target. Additionally, RNA pull-down assay was performed to explore the physical association between miR-137, SNHG1, and RNA induced silencing complex (RISC). Cell cycling and invasion were examined by flow cytometry (FCM) and transwell assays. The in vivo carcinogenic activity of SNHG1 was examined using murine xenograft models. Expression of RICTOR, serine/threonine kinase 1 (AKT), serum and glucocorticoid-inducible kinase 1 (SGK1), p70S6K1, and LC3II/LC3I ratio was examined by Western blot analysis. SNHG1 upregulation was observed in CRC tissues and cell lines, which was associated with the lymph node metastasis, advanced TNM stage and poorer prognosis. SNHG1 increased RICTOR level in CRC via sponging miR-137. In addition, SNHG1 silencing inhibited CRC cell proliferation and migration in vitro and in vivo. SNHG1 regulated RICTOR expression by sponging miR-137 and promoted tumorgenesis in CRC.