长链非编码 RNA SNHG14 通过调控 miR-876-5p/SSR2 轴促进肝癌进展。

Long noncoding RNA SNHG14 promotes hepatocellular carcinoma progression by regulating miR-876-5p/SSR2 axis.

机构信息

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China.

Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, P. R. China.

出版信息

J Exp Clin Cancer Res. 2021 Jan 23;40(1):36. doi: 10.1186/s13046-021-01838-5.

BACKGROUND

Aberrant expressions of long noncoding RNAs (lncRNAs) have been demonstrated to be related to the progress of HCC. The mechanisms that SNHG14 has participated in the development of HCC are obscure.

METHODS

Quantitative real-time PCR (qRT-PCR) was used to measure the lncRNA, microRNA and mRNA expression level. Cell migration, invasion and proliferation ability were evaluated by transwell and CCK8 assays. The ceRNA regulatory mechanism of SNHG14 was evaluated by RNA immunoprecipitation (RIP) and dual luciferase reporter assay. Tumorigenesis mouse model was used to explore the roles of miR-876-5p in vivo. The protein levels of SSR2 were measured by western blot assay.

RESULTS

In this study, we demonstrated that SNHG14 was highly expressed in HCC tissues, meanwhile, the elevated expression of SNHG14 predicted poor prognosis in patients with HCC. SNHG14 promoted proliferation and metastasis of HCC cells. We further revealed that SNHG14 functioned as a competing endogenous RNA (ceRNA) for miR-876-5p and that SSR2 was a downstream target of miR-876-5p in HCC. Transwell, CCK8 and animal experiments exhibited miR-876-5p inhibited HCC progression in vitro and in vivo. By conducting rescue experiments, we found the overexpression of SSR2 or knocking down the level of miR-876-5p could reverse the suppressive roles of SNHG14 depletion in HCC.

CONCLUSION

SNHG14 promotes HCC progress by acting as a sponge of miR-876-5p to regulate the expression of SSR2 in HCC.

背景

长链非编码 RNA（lncRNA）的异常表达与 HCC 的进展有关。SNHG14 参与 HCC 发展的机制尚不清楚。

方法

采用定量实时 PCR（qRT-PCR）测定 lncRNA、microRNA 和 mRNA 的表达水平。通过 Transwell 和 CCK8 测定细胞迁移、侵袭和增殖能力。通过 RNA 免疫沉淀（RIP）和双荧光素酶报告基因测定评估 SNHG14 的 ceRNA 调控机制。采用肿瘤生成小鼠模型在体内探索 miR-876-5p 的作用。通过 Western blot 测定 SSR2 的蛋白水平。

结果

本研究表明，SNHG14 在 HCC 组织中高表达，同时 SNHG14 的高表达预示着 HCC 患者的预后不良。SNHG14 促进 HCC 细胞的增殖和转移。我们进一步揭示 SNHG14 作为 miR-876-5p 的竞争性内源性 RNA（ceRNA）发挥作用，SSR2 是 miR-876-5p 在 HCC 中的下游靶标。Transwell、CCK8 和动物实验表明 miR-876-5p 在体外和体内抑制 HCC 的进展。通过进行挽救实验，我们发现 SSR2 的过表达或 miR-876-5p 水平的敲低可以逆转 SNHG14 耗竭对 HCC 的抑制作用。