lncRNA TINCR attenuates the proliferation and invasion, and enhances the apoptosis of cutaneous malignant melanoma cells by regulating the miR‑424‑5p/LATS1 axis.

Content Provider	Europe PMC
Author	Han, Xuemei Jia, Yuxi Chen, Xiangru Sun, Chengkuan Sun, Jing
Copyright Year	2021
Abstract	Cutaneous malignant melanoma (CMM) is responsible for ≥1/2 of skin cancer-related mortalities. The aberrant expression of long non-coding RNAs (lncRNAs) has been associated with the development of CMM. However, to the best of our knowledge, the role of the lncRNA TINCR ubiquitin domain containing (TINCR) in CMM has not been previously investigated, and thus, the current study aimed to evaluate this in vitro and in vivo. Reverse transcription-quantitative PCR (RT-qPCR) was used to analyze microRNA (miR)-424-5p expression, and RT-qPCR and western blotting were used to measure TINCR, large tumor suppressor kinase 1 (LATS1), cellular communication network factor 2 (CTGF), cellular communication network factor 1 (CCN1) and AXL receptor tyrosine kinase (AXL) mRNA and protein expression levels, respectively. Cell Counting Kit-8, flow cytometry and Transwell assays were used to detect the proliferation, apoptosis and invasion of CMM cell lines, respectively. The binding sites between TINCR and miR-424-5p were predicted using the miRDB database. A dual luciferase reporter assay and RT-qPCR were used to identify the relationship between TINCR and miR-424-5p in CMM cell lines. The bioinformatics analysis revealed that TINCR was one of the most significantly downregulated lncRNAs in CMM, and advanced stage CMM tissues showed the greatest decrease in TINCR expression. Moreover, in the collected CMM tissues and tested cell lines of the current study, TINCR expression was found to be downregulated compared with the respective controls. Notably, TINCR overexpression inhibited the expression levels of CTGF, CCN1 and AXL, decreased the proliferation and invasion, and induced the apoptosis of CMM cell lines. In addition, a mutual binding association was identified between miR-424-5p and TINCR in CMM cells. LATS1, a target of miR-424-5p, was found to be positively regulated by TINCR. TINCR activated Hippo signaling and repressed the activity of Yes 1 associated transcriptional regulator by regulating LATS1 expression, while LATS1 knockdown reversed the effect of TINCR overexpression on CMM cells. Collectively, the findings of the present study suggested that TINCR may attenuate the progression of CMM by regulating the miR-424-5p/LATS1 signaling axis. These results indicated that TINCR may play a tumor suppressive role in CMM.
ISSN	1021335X
Journal	Oncology Reports
Volume Number	46
PubMed Central reference number	PMC8485017
Issue Number	5
PubMed reference number	34542165
e-ISSN	17912431
DOI	10.3892/or.2021.8189
Language	English
Publisher	D.A. Spandidos
Publisher Date	2021-09-20
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Han et al.
Subject Keyword	cutaneous malignant melanoma long non-coding RNA TINCR ubiquitin domain containing microRNA-424-5p/large tumor suppressor kinase 1 axis cell proliferation cell apoptosis
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology