Long non-coding RNA HAGLROS regulates lipid metabolism reprogramming in intrahepatic cholangiocarcinoma via the mTOR signaling pathway

Alternation of long non-coding RNA (lncRNA) is implicated in intrahepatic cholangiocarcinoma (ICC) development. HAGLROS is a lncRNA with a length of 699 bp, which is involved in the progression of various cancers. But the mechanism of HAGLROS in ICC remains unknown. In this study, the sh-HAGLROS-1 or sh-HAGLROS-2 was transfected into QBC939 cells, and overexpressing HAGLROS vector was transfected into KMCH cells. HAGLROS expression in ICC tissues and cell lines was detected, and its association with ICC prognosis was further analyzed. Lipid accumulation and lipid-related indicators (TG, LDL-C, TC and HDLC) in QBC939 and KMCH cells were measured. ICC cell viability, invasion and migration were measured. Western blot analysis was used to detect levels of the mTOR axis-related proteins and autophagy-related proteins (LC3I, LC3II, Beclin and P62). The levels of serum lipids and SREBP1 positive expression in transplanted tumors of nude mice were detected. HAGLROS was highly expressed in ICC and negatively correlated with prognosis. QBC939 cells with knocking down HAGLROS exhibited reduced lipid-related protein levels, blocked ICC cellular processes, inactivated mTOR axis, and increased autophagy. QBC939 cells with overexpressing HAGLROS showed opposite trends. The lipid-related protein levels in serum of nude mice and SREBP1 positive expression in transplanted tumors were diminished. Taken together, sh-HAGLROS inactivated the mTOR axis and promoted autophagy, thereby improving lipid metabolism reprogramming in ICC. This study may offer novel ICC treatments.