The LINC00519/hsa-miR-22-3p/MECOM Axis Accelerates Intrahepatic Cholangiocarcinoma Progression Through PI3K/AKT Signaling.

Abstract

Intrahepatic cholangiocarcinoma (ICC) is the second most common liver cancer. LINC00519 plays prominent roles in the progression of numerous cancers. To explore the molecular mechanism of LINC00519 in ICC, LINC00519, hsa-miR-22-3p, and MECOM expressions in ICC were assessed with ENCORI database and quantitative real-time PCR. Biological functions of LINC00519 in ICC were examined using clone formation experiment, Transwell analysis, flow cytometry, and Western blot. Meanwhile, the LINC00519 mechanism in ICC was determined by dual-luciferase reporter assay. Results showed that LINC00519 and MECOM were highly expressed in ICC, but hsa-miR-22-3p was decreased. Functionally, silencing LINC00519 weakened ICC cell proliferation, migration and induced cell apoptosis. Also, LINC00519 knockdown repressed PI3K/AKT pathway. Mechanistically, LINC00519 acted as a competitive endogenous RNA to target MECOM by sponging hsa-miR-22-3p. Meanwhile, rescue assays further proved that low LINC00519 expression restrained ICC cell proliferation and migration, and accelerated apoptosis through PI3K/AKT pathway by miR-22-3p/MECOM. In conclusion, this research revealed a novel LINC00519/hsa-miR-22-3p/MECOM regulatory axis and PI3K/AKT pathway that modulated ICC progression. Implications: This study deepens the understanding of the non-coding RNA regulatory network in ICC and provides potential targets for the diagnosis and targeted therapy of ICC.