Long non-coding RNA JPX promotes gastric cancer progression by regulating CXCR6 and autophagy via inhibiting miR-197

摘要

Long non-coding RNAs (lncRNAs) serve a crucial role in gastric cancer (GC) progression. However, the molecular mechanism underlying lncRNA JPX transcript, XIST activator (JPX) in the tumorigenesis of GC is not completely understood. Reverse transcription-quantitative PCR (RT-qPCR) and western blotting were performed to detect gene expression. A luciferase reporter gene assay was conducted to determine the relationship between microRNA (miR)-197 and JPX or C-X-C motif chemokine receptor 6 (CXCR6). Cell viability, migration and invasion were determined by performing MTT, wound healing and Transwell assays, respectively. The Cancer Genome Atlas database and the RT-qPCR results indicated that JPX expression was upregulated and miR-197 expression was downregulated in patients with GC and in GC cells. Moreover, high JPX expression and low miR-197 expression in patients with GC indicated poor prognosis. miR-197 expression was directly inhibited by JPX. Compared with the short hairpin RNA (sh) negative control (NC) group, NCI-N87 and MKN-45 cells in the shJPX group displayed decreased cell viability and invasion, as well as a wider scratch width. NCI-N87 and MKN-45 cells in the shJPX + miR-197 inhibitor group had increased viability and invasion, but a narrower scratch width compared with the shJPX group. It was also identified that miR-197 directly inhibited CXCR6 expression. miR-197 inhibited Beclin1 protein expression and promoted p62 protein expression. Compared with the NC group, NCI-N87 and MKN-45 cells in the miR-197 mimic group had decreased cell viability and invasion, and a wider scratch width. Enhanced cell viability and invasion, and a narrower scratch width was also observed in the miR-197 mimic + CXCR6 and miR-197 mimic + Beclin1 groups, compared with the miR-197 mimic group. Collectively, the results indicated that lncRNA JPX promoted GC progression by regulating CXCR6 and autophagy via inhibiting miR-197. Furthermore, JPX knockdown regulated GC cell phenotype by promoting miR-197.