LncRNA SNHG12通过miR-129-5p/GTPBP4对肝细胞癌进展的促进作用  

Long non-coding RNA SNHG12 promotes progression of hepatocellular carcinoma through miR-129-5p/GTPBP4

作　　者：章诺贝[1] 沈浩[1] 黄神安[1] 陈新[2] ZHANG Nuobei;SHEN Hao;HUANG Shen’an;CHEN Xin(Department of Gastroenterology,Second Affiliated Hospital of Nanchang University,Nanchang,Jiangxi Province,330000,China;Department of Nuclear Medicine,Second Affiliated Hospital of Nanchang University,Nanchang,Jiangxi Province,330000,China)

机构地区：[1]南昌大学第二附属医院消化内科,南昌330000 [2]南昌大学第二附属医院核医学科,南昌330000

出　　处：《第三军医大学学报》2021年第18期1783-1795,共13页Journal of Third Military Medical University

基　　金：国家自然基金地区科学基金项目(81760427);江西省自然科学基金(20202BABL206094,20202BABL216037);江西省卫生健康委科技计划(20201037,202110042)。

摘　　要：目的探讨长链非编码RNA(LncRNA)核仁小RNA宿主基因12(small nucleolar RNA host gene 12, SNHG12)对肝细胞癌(hepatocellular carcinoma, HCC)发展的调控机制。方法通过RT-qPCR检测长链非编码RNA(long noncoding RNA, LncRNA) SNHG12在肝癌组织和肝癌细胞系中的表达水平;分析肝癌组织中LncRNA SNHG12的表达水平与HCC患者临床病理参数的关系;运用MTT实验、细胞集落形成实验、Transwell实验、划痕愈合实验、裸鼠成瘤实验检测LncRNA SNHG12、miR-129-5p、GTPBP4在肝癌细胞活性、增殖、迁移、侵袭中的作用;采用荧光素酶报告基因、RT-qPCR、Western blot实验来评估LncRNA SNHG12、miR-129-5p、GTPBP4之间的互相作用。结果 LncRNA SNHG12在肝癌组织和肝癌细胞系中表达上调(P<0.05);LncRNA SNHG12表达水平较高的HCC患者相比其表达水平较低的患者预后更差(P<0.05);LncRNA SNHG12表达水平与肿瘤大小、TNM分期、淋巴结转移存在正相关的关系;LncRNA SNHG12可促进HCC的细胞活性、增殖、迁移及侵袭(P<0.05);miR-129-5p在肝癌组织中表达下调,其可抑制肝癌细胞活性、增殖、迁移及侵袭(P<0.05);LncRNA SNHG12可通过与miR-129-5p进行竞争性结合,从而促进GTPBP4的表达(P<0.05);GTPBP4在HCC组织中表达上调,其可促进肝癌细胞活性、增殖、迁移及侵袭(P<0.05)。结论 LncRNA SNHG12可通过调控miR-129-5p/GTPBP4轴从而促进HCC的进展。Objective To explore the regulatory mechanism of long non-coding RNA(LncRNA) small nucleolar RNA host gene 12(SNHG12) on the development of hepatocellular carcinoma(HCC). Methods The expression levels of SNHG12 in HCC tissues as well as in HCC cell lines were detected by RT-qPCR, and the correlation between the SNHG12 level and the clinicopathological parameters of HCC patients was then analyzed. The effects of SNHG12, miR-129-5 p and GTPBP4 on the activity, proliferation, migration and invasion of HCC cells were determined using MTT assay, cell colony formation test, Transwell test, scratch healing assay and xenograft tumor growth assay, respectively. Finally, luciferase reporter gene, RT-qPCR and Western blotting were employed to evaluate the interactions among SNHG12, miR-129-5 p and GTPBP4. Results The expression of SNHG12 was up-regulated in both HCC tissues and HCC cell lines(P<0.05). HCC patients with higher expression level of SNHG12 had a worse prognosis than those with lower level(P<0.05), and its level was positively correlated with tumor size, TNM stage and lymph node metastasis. LncRNA SNHG12 promoted the viability, proliferation, migration and invasion of HCC cells(P<0.05), whereas, miR-129-5 p was down-regulated in HCC tissues and showed inhibitory effects on above biological behaviors of HCC cells(P<0.05). Moreover, through competitively binding with miR-129-5 p, SNHG12 promoted GTPBP4 expression(P<0.05), which was up-regulated in HCC tissues and facilitated the activity, proliferation, migration and invasion of HCC cells(P<0.05). Conclusion LncRNA SNHG12 promotes the progression of HCC by regulating the miR-129-5 p/GTPBP4 axis.

关 键 词：肝细胞癌 LncRNA SNHG12 miR-129-5p GTPBP4 

分 类 号：R394.3[医药卫生—医学遗传学] R730.23[医药卫生—基础医学]