LBX2-AS1 promotes ovarian cancer progression by facilitating E2F2 gene expression via miR-455-5p and miR-491-5p sponging.

Abstract

LBX2-AS1 is a long non-coding RNA that facilitates the development of gastrointestinal cancers and lung cancer, but its participation in ovarian cancer development remained uninvestigated. Clinical data retrieved from TCGA ovarian cancer database and the clinography of 60 ovarian cancer patients who received anti-cancer treatment in our facility were analysed. The overall cell growth, colony formation, migration, invasion, apoptosis and tumour formation on nude mice of ovarian cancer cells were evaluated before and after lentiviral-based LBX2-AS1 knockdown. ENCORI platform was used to explore LBX2-AS1-interacting microRNAs and target genes of the candidate microRNAs. Luciferase reporter gene assay and RNA pulldown assay were used to verify the putative miRNA-RNA interactions. Ovarian cancer tissue specimens showed significant higher LBX2-AS1 expression levels that non-cancerous counterparts. High expression level of LBX2-AS1 was significantly associated with reduced overall survival of patients. LBX2-AS1 knockdown significantly down-regulated the cell growth, colony formation, migration, invasion and tumour formation capacity of ovarian cancer cells and increased their apoptosis in vitro. LBX2-AS1 interacts with and thus inhibits the function of miR-455-5p and miR-491-5p, both of which restrained the expression of E2F2 gene in ovarian cancer cells via mRNA targeting. Transfection of miRNA inhibitors of these two miRNAs or forced expression of E2F2 counteracted the effect of LBX2-AS1 knockdown on ovarian cancer cells. LBX2-AS1 was a novel cancer-promoting lncRNA in ovarian cancer. This lncRNA increased the cell growth, survival, migration, invasion and tumour formation of ovarian cancer cells by inhibiting miR-455-5p and miR-491-5p, thus liberating the expression of E2F2 cancer-promoting gene.

• Authors: Jian Cao, Huan Wang, Guangquan Liu, Ranran Tang, Ye Ding, Pengfei Xu, Huayu Wang, Juan Miao, Xiaoyan Gu, Suping Han
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 25 Issue 2 Pg. 1178-1189 (01 2021) ISSN: 1582-4934 [Electronic] England
• PMID: 33342041 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• 3' Untranslated Regions
• E2F2 Transcription Factor
• MIRN455 microRNA, human
• MIRN491 microRNA, human
• MicroRNAs
• RNA, Long Noncoding

Topics

• 3' Untranslated Regions (genetics)
• Base Sequence
• Cell Line, Tumor
• Disease Progression
• E2F2 Transcription Factor (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs (genetics, metabolism)
• Models, Biological
• Ovarian Neoplasms (genetics, pathology)
• RNA, Long Noncoding (genetics, metabolism)
• Survival Analysis