Long non‑coding RNA XIST promotes cell proliferation of pancreatic cancer through miR‑137 and Notch1 pathway.

OBJECTIVE

Long non-coding ribonucleic acids X-inactive specific transcript (lncRNA XIST) is one lncRNAs which involved in multiple human cancers. However, the functions and potential molecular regulatory mechanisms of XIST/microRNA-137 (miR‑137) in pancreatic cancer (PC) still need to explore.

PATIENTS AND METHODS

PC tissues and cell lines were analyzed for XIST, miR-137 and Notch1 expressions through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Nude mouse xenograft tumor assay was used to detect XIST effects on pancreatic tumorigenesis in vivo. Cell Counting Kit (CCK-8) assay was performed to detect PC cell proliferation. Dual-Luciferase reporter assay, qRT-PCR, RNA immunoprecipitation (RIP) and Western blot assays were applied to validate the target relationship of XIST, miR‑137 and Notch1.

RESULTS

Results demonstrated that XIST expression was increased in PC tissues and cells. XIST knockdown inhibited PC cell proliferation in vitro and also repressed the tumor growth in vivo. XIST directly interacted with miR-137 and negatively regulated its expression. Notch1 was identified as a target gene of miR-137 and XIST acted as a competitive endogenous RNA (ceRNA) to positively regulate Notch1 expression by suppressing miR-137. In addition, we detected miR-137 was negatively correlated with XIST and Notch1 respectively, and a positive correlation between Notch1 and XIST expression in PC tissues. Furthermore, Notch1 overexpression could offset the suppressing effect of XIST knockdown or miR-137 overexpression on cell proliferation. Therefore, XIST may play an important role in promoting cell proliferation through miR‑137 and Notch1 pathway in PC.

CONCLUSIONS

To sum up, these results proposed that XIST functioned as an endogenous sponge in promoting PC cell proliferation through competing for miR-137 to regulate Notch1 expression, and may provide more therapeutic targets for the patients with PC.