The lncRNA XIST promotes proliferation, migration and invasion of gastric cancer cells by targeting miR-337

Background and study aims: Gastric cancer (GC) is one of the most common malignant tumours worldwide. Long non-coding RNAs (lncRNAs) and microRNAs regulate the occurrence and development of various cancers and play an important role in GC progression. X-inactive specific transcript (XIST), a carcinogenic lncRNA, is involved in human tumourigenesis and is altered in GC. Janus kinase 2 (JAK2), a transcription factor, is involved in cancer cell metastasis and differentiation. However, the exact mechanism underlying the biological roles of XIST and JAK2 in cancer cells remains unclear.

Material and methods: This study was conducted using GES-1, HGC-27, AGS and HEK-293 T cells. Quantitative polymerase chain reaction and western blotting were performed to detect XIST, microRNA-337 (miR-337) and JAK2 expressions. GC cell invasion was investigated by using the Transwell assay. Fluorescein reporter gene detection was used to determine the relationship between JAK2 and XIST.

Results: Compared with that in GES-1 cells, XIST expression was significantly up-regulated in AGS and HGC-27 cells. miR-337 expression in GC cell lines was decreased. The proliferation, invasion and migration of GC cells were simultaneously inhibited by XIST knockdown, and the relationship between XIST and miR-337 was confirmed by bioinformatics analysis. JAK2 is expected to be the target gene of miR-337. MiR-337 can negatively regulate JAK2 expression in vitro. In addition, si-XIST decreased JAK2 expression by up-regulating miR-337 in vitro, thereby inhibiting GC cell proliferation and migration. Therefore, we speculated that XIST regulates JAK2 by competing with miR-337 as a competitive endogenous lncRNA in GC.

Conclusion: We elucidated the effects of migration and invasion after XIST inhibition, at least in part, by inhibiting miR-337 expression in GC cells to regulate JAK2. These data indicate that a positive feedback loop exists between XIST and JAK2 and suggest that JAK2 and XIST play a vital role in cancer cell migration and invasion.