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

Abstract

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.

• Authors: Hai-Ting Liu, Ran-Ran Ma, Bei-Bei Lv, Hui Zhang, Duan-Bo Shi, Xiang-Yu Guo, Guo-Hao Zhang, Peng Gao
• Journal: British journal of cancer (Br J Cancer) Vol. 122 Issue 12 Pg. 1825-1836 (06 2020) ISSN: 1532-1827 [Electronic] England
• PMID: 32336754 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN30b microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• long non-coding RNA HNF1A-AS1, human
• Proto-Oncogene Proteins c-akt

Topics

• Aged
• Animals
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Heterografts
• Humans
• Male
• Mice
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Long Noncoding (genetics, metabolism)
• Signal Transduction (physiology)
• Stomach Neoplasms (genetics, metabolism, pathology)