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

Abstract

Cutaneous malignant melanoma (CMM) is respon- sible 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 bioinfor- matics 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 find- ings 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.