lncRNA HIT000218960 enhances resistance to 5-fluorouracil by promoting HMGA2 and activating the AKT/mTOR/P70S6K pathway in gastric cancer cells.

The aim of the present study was to investigate the effect of the long noncoding RNA HIT000218960 on gastric cancer cell resistance to 5-fluorouracil (5-FU) and to explore the underlying molecular mechanism. HIT000218960 expression was measured in gastric cancer tissues and cells lines using reverse transcription-quantitative PCR and western blotting. Gastric cancer cell lines with overexpressed or repressed HIT000218960 levels were generated to study its influence on apoptosis induced by 5-FU, which was analyzed using flow cytometry analysis. Compared with those in normal gastric mucosal tissues and non-cancerous gastric mucosal epithelial cells, HIT000218960 and high mobility group A2 (HMGA2) proteins were found to be upregulated in gastric cancer tissues and cells. Additionally, a positive correlation was found between the expression of HIT000218960 and HMGA2 in gastric cancer tissues. In patients with gastric cancer, HIT000218960 expression was revealed to associate negatively with the efficacy of chemotherapy and 3-year overall survival rate. Overexpression of HIT000218960 suppressed apoptosis in SNU-5 cells, whilst HIT000218960 knockdown increased the apoptosis of NCI-N87 cells following 5-FU treatment. Downstream, HIT000218960 was demonstrated to promote HMGA2 protein expression in gastric cancer cells. In these cells, knocking down HMGA2 expression significantly increased apoptosis in addition to reducing AKT, mTOR and P70S6 kinase (P70S6K) phosphorylation after 5-FU treatment. In conclusion, HIT000218960 is overexpressed in gastric cancer tissues and cells, which is associated with the efficacy of chemotherapy. Mechanistically, this may be mediated by the upregulation HMGA2 expression and AKT/mTOR/P70S6K signaling.