Affiliations: [a] Department of General Surgery, The Fourth Medical Center of PLA General Hospital, Beijing, China | [b] Key Laboratory of Tissue Repair and Regeneration of PLA and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Fourth Medical Center of General Hospital of PLA, Beijing, China | [c] Fourth Medical Center of PLA General Hospital, Beijing, China
Correspondence:
[*]
Corresponding author: Fei-De Liu, Department of General Surgery, The Fourth Medical Center of PLA General Hospital, Beijing 100048, China. E-mail: [email protected].
Note: [1] These authors contributed equally to this work as the co-first authors.
Abstract: Gastric cancer (GC) remains poor prognosis and survival issues due to the resistance of chemotherapies, such as cisplatin. The long non-coding RNA small nucleolar RNA host gene 7 (lncRNA-SNHG7) is known as an oncogenic molecule in diverse cancers. Here, we demonstrate that SNHG7 was significantly upregulated in gastric cancer and positively correlated with cisplatin resistance of gastric cancer cells that SNHG7 was significantly upregulated in cisplatin resistant cells. Silencing SNHG7 dramatically sensitized cisplatin resistant cells. In contrast, a negative correlation between lncRNA-SNHG7 and miR-34a was found that miR-34a was downregulated in gastric cancer patient tissues and significantly sensitized cisplatin resistant gastric cancer cells. Intriguingly, bioinformatical analysis indicated miR-34a has putative biding site for SNHG7 and such negative association between SNHG7 and miR-34a was verified in gastric cancer tissues. The cisplatin resistant cells displayed increased glycolysis rate and SNHG7 promoted cellular glycolysis rate of gastric cancer cells. Luciferase assay illustrated LDHA, a glycolysis enzyme, was the direct target of miR-34a. Importantly, inhibiting SNHG7 successfully suppressed LDHA expressions and sensitized cisplatin resistant cells and such inhibitory effects could be recovered by further anti-miR-34a. These findings suggest an important regulator mechanism for the SNHG7-mediated cisplatin resistance via miR-34a/LDHA-glycolysis axis.
