长链非编码 RNA-HNF1A-AS1 通过海绵吸附 miR-30b-3p 作为竞争性内源性 RNA 激活胃癌中的 PI3K/AKT 信号通路。

LncRNA-HNF1A-AS1 functions as a competing endogenous RNA to activate PI3K/AKT signalling pathway by sponging miR-30b-3p in gastric cancer.

机构信息

Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, P. R. China.

Department of Pathology, Shandong Provincial Hospital affiliated to Shandong university, Jinan, P. R. China.

出版信息

Br J Cancer. 2020 Jun;122(12):1825-1836. doi: 10.1038/s41416-020-0836-4. Epub 2020 Apr 27.

BACKGROUND

Accumulating evidence demonstrated that long noncoding RNAs (lncRNAs) played important regulatory roles in many cancer types. However, the role of lncRNAs in gastric cancer (GC) progression remains unclear.

METHODS

RT-qPCR assay was performed to detect the expression of HNF1A-AS1 in gastric cancer tissues and the non-tumourous gastric mucosa. Overexpression and RNA interference approaches were used to investigate the effects of HNF1A-AS1 on GC cells. Insight into competitive endogenous RNA (ceRNA) mechanisms was gained via bioinformatics analysis, luciferase assays and an RNA-binding protein immunoprecipitation (RIP) assay, RNA-FISH co-localisation analysis combined with microRNA (miRNA)-pulldown assay.

RESULTS

This study displayed that revealed expression of HNF1A-AS1 was associated with positive lymph node metastasis in GC. Moreover, HNF1A-AS1 significantly promoted gastric cancer invasion, metastasis, angiogenesis and lymphangiogenesis in vitro and in vivo. In addition, HNF1A-AS1 was demonstrated to function as a ceRNA for miR-30b-3p. HNF1A-AS1 abolished the function of the miRNA-30b-3p and resulted in the derepression of its target, PIK3CD, which is a core oncogene involved in the progression of GC.

CONCLUSION

This study demonstrated that HNF1A-AS1 worked as a ceRNA and promoted PI3K/AKT signalling pathway-mediated GC metastasis by sponging miR-30b-3p, offering novel insights of the metastasis mechanism in GC.

背景

越来越多的证据表明，长非编码 RNA（lncRNA）在多种癌症类型中发挥重要的调控作用。然而，lncRNA 在胃癌（GC）进展中的作用尚不清楚。

方法

通过 RT-qPCR 检测胃癌组织和非肿瘤性胃黏膜中 HNF1A-AS1 的表达。采用过表达和 RNA 干扰方法研究 HNF1A-AS1 对 GC 细胞的影响。通过生物信息学分析、荧光素酶报告基因实验和 RNA 结合蛋白免疫沉淀（RIP）实验，以及 RNA-FISH 共定位分析结合 miRNA 下拉实验，深入了解竞争性内源性 RNA（ceRNA）机制。

结果

本研究表明 HNF1A-AS1 的表达与 GC 中的阳性淋巴结转移有关。此外，HNF1A-AS1 显著促进了体外和体内胃癌的侵袭、转移、血管生成和淋巴管生成。此外，HNF1A-AS1 被证明是 miR-30b-3p 的 ceRNA。HNF1A-AS1 消除了 miRNA-30b-3p 的功能，导致其靶基因 PIK3CD 的去抑制，PIK3CD 是参与 GC 进展的核心癌基因。