Long non-coding RNA TTN-AS1 regulates the proliferation, invasion and migration of triple-negative breast cancer by targeting miR-211-5p

Abstract

Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) serve important roles in numerous malignancies, including triple-negative breast cancer (TNBC). The lncRNA titin-antisense RNA1 (TTN-AS1) has previously been reported to promote tumorigenesis in various types of cancer. The present study aimed to investigate the potential role of TTN-AS1 in breast cancer and the associated underlying mechanisms. Following prediction by Starbase and confirmation by dual-luciferase reporter assay, TINCR was demonstrated to be a target gene for microRNA (miR)-211-5p. The expression levels of TTN-AS1 and miR-211-5p, which was predicted to be targeted by TTN-AS1, in TNBC tissues and in the breast cancer cell lines MDA-MB-453 and MDA-MB-231 were measured using reverse transcription-quantitative PCR. Following TTN-AS1-knockdown, cell proliferation was measured using a Cell Counting Kit-8 assay and colony formation assay, whereas cell invasion and migration were measured using Transwell and wound healing assays, respec- tively. Luciferase reporter assay was performed to verify the potential interaction between TTN-AS1 and miR-211-5p. In addition, rescue assays were conducted to investigate the effects of TTN-AS1 and miR-211-5p on TNBC development. The results demonstrated that TTN-AS1 expression was signif- icantly upregulated, whereas that of miR-211-5p was found to be downregulated in TNBC tissues and cell lines compared with the matched adjacent normal tissues and normal breast epithelial cell line MCF-10A, respectively. Furthermore, TTN-AS1-knockdown inhibited the proliferation and invasive and migratory abilities of MDA-MB-453 and MDA-MB-231 cells, which was reversed following co-transfection with the miR-211-5p inhibitor. The results from luciferase reporter assay confirmed that miR-211-5p was a direct target of TTN-AS1, suggesting that TTN-AS1 may bind directly to miR-211-5p to negatively regulate its expression. In conclusion, the findings from the present study demonstrated that TTN-AS1 regulated the proliferation and invasive and migratory abilities of TNBC by targeting miR-211-5p. This study may provide some insights into the regulatory mechanism of TNBC and help the develop- ment of novel therapeutic interventions for TNBC.