SNHG15 promotes gallbladder cancer progression by enhancing the autophagy of tumor cell under nutrition stress

ABSTRACT

Gallbladder cancer (GBC) is a major malignant carcinoma of the biliary tract with extremely poor prognosis. Currently, there is no useful therapy strategies for GBC treatment, indicating the unmet mechanism researches for GBC. In this study, our data showed that SNHG15 expression significantly up-regulated and its high expression associated with poor overall survival of patients suffer from GBC. Functional experiments showed that SNHG15 depletion delayed the proliferation and enhanced the apoptosis of GBC tumor cells under the nutrition stress condition, which further confirmed in the subcutaneous xenograft model and liver metastasis model. Mechanistically, SNHG15 could interact with AMPK and facilitate the phosphorylation of AMPK to Tuberous sclerosis complex TSC2, resulting in mTOR suppression and autophagy enhancement, and finally, conferring the GBC cell sustain proliferation under nutrition stress. Taken together, our findings revealed that SNHG15 promotes GBC tumor progression by enhancing the autophagy under poor nutrition tumor microenvironment, which could be a promising targets for GBC.

KEYWORDS:

• Gallbladder cancer
• SNHG15
• autophagy
• TSC2

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contribution

H.M., L.H.Y, X.X conducted experiments and collected the data; H.M., L.H.Y, X.X performed experiments and provided intellectual discussion. H.M., Y.G., F.L. designed the experiments. H.M., Y.B. L. wrote the manuscript. All authors critically revised and approved the manuscript.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.