Journal
MOLECULAR CANCER
Volume 18, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12943-019-1097-9
Keywords
Gallbladder cancer; lncRNA-HGBC; miR-502-3p; SET; HuR
Categories
Funding
- National Natural Science Foundation of China [31601021, 31620103910, 81874181, 91440203, 81772512, 81672404]
- Emerging Frontier Program of Hospital Development Center [SHDC12018107]
- General Surgery Construction Program of Shanghai Municipal Health Commission [2017ZZ02011]
- Xinhua Hospital PI-startup funds [JZPI201716]
- Shanghai Municipal Health and Family Planning Commission [2018YQ10]
- Shanghai Municipal Human Resources and Social Security Bureau [2018048]
- Shanghai Pujiang Program [17PJ1406100]
- Shanghai Key Laboratory of Biliary Tract Disease Research Foundation [17DZ2260200]
Ask authors/readers for more resources
Backgrounds Long non-coding RNAs (lncRNAs) are essential factors that regulate tumor development and metastasis via diverse molecular mechanisms in a broad type of cancers. However, the pathological roles of lncRNAs in gallbladder carcinoma (GBC) remain largely unknown. Here we discovered a novel lncRNA termed lncRNA Highly expressed in GBC (lncRNA-HGBC) which was upregulated in GBC tissue and aimed to investigate its role and regulatory mechanism in the development and progression of GBC. Methods The expression level of lncRNA-HGBC in GBC tissue and different cell lines was determined by quantitative real-time PCR. The full length of lncRNA-HGBC was obtained by 5 ' and 3 ' rapid amplification of the cDNA ends (RACE). Cellular localization of lncRNA-HGBC was detected by fluorescence in situ hybridization (FISH) assays and subcellular fractionation assay. In vitro and in vivo assays were preformed to explore the biological effects of lncRNA-HGBC in GBC cells. RNA pull-down assay, mass spectrometry, and RNA immunoprecipitation (RIP) assay were used to identify lncRNA-HGBC-interacting proteins. Dual luciferase reporter assays, AGO2-RIP, and MS2-RIP assays were performed to verify the interaction between lncRNA-HGBC and miR-502-3p. Results We found that lncRNA-HGBC was upregulated in GBC and its upregulation could predict poor survival. Overexpression or knockdown of lncRNA-HGBC in GBC cell lines resulted in increased or decreased, respectively, cell proliferation and invasion in vitro and in xenografted tumors. LncRNA-HGBC specifically bound to RNA binding protein Hu Antigen R (HuR) that in turn stabilized lncRNA-HGBC. LncRNA-HGBC functioned as a competitive endogenous RNA to bind to miR-502-3p that inhibits target gene SET. Overexpression, knockdown or mutation of lncRNA-HGBC altered the inhibitory effects of miR-502-3p on SET expression and downstream activation of AKT. Clinically, lncRNA-HGBC expression was negatively correlated with miR-502-3p, but positively correlated with SET and HuR in GBC tissue. Conclusions Our study demonstrates that lncRNA-HGBC promotes GBC metastasis via activation of the miR-502-3p-SET-AKT cascade, pointing to lncRNA-HGBC as a new prognostic predictor and a therapeutic target.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available