Experimental Study
Regulatory mechanism of long non-coding RNA HULC in promoting cholangiocarcinoma cell migration and invasion
Hua Ye, Bo He, Jie Chen, Chuanchao He, Yibiao Ye, Tao Chen
Published 2019-08-08
Cite as Chin J Exp Surg, 2019, 36(8): 1401-1405. DOI: 10.3760/cma.j.issn.1001-9030.2019.08.019
Abstract
ObjectiveTo understand long non-coding RNAs (lncRNAs) in the pathogenesis of cholangiocarcinoma (CCA) and to explore the novel therapeutic strategies for improving disease outcome.
MethodsWe firstly reanalyzed 5 RNA-Seqs from GEO database, and identified 20 lncRNAs responding to oxidative stress or inflammatory response. Quantitative Real-time PCR was used to identify aberrantly expressed lncRNA HULC. Small interfering RNA and overexpressed plasmids were used to modulate the expression of HULC , and luciferase target assay and RNA immunoprecipitaion (RIP) were performed to explore the mechanism of the lncRNAs.
ResultsWe firstly analyzed available RNA-seqs datasets to investigate aberrantly expressed lncRNAs which might been associated with inflammation or oxidative stress. We identified that lncRNA HULC was differentially expressed among all the samples under the treatment of hypoxic or inflammatory factors, and they were shown to be simulated by short-term oxidative stress responses to H2O2 and glucose oxidase in CCA cell lines (t=8.709, P<0.01); Further studies revealed that the lncRNA HULC promoted cholangiocyte migration and invasion via the inflammation pathway (t=9.183, P<0.01). lncRNA HULC functioned as competing endogenous RNAs (ceRNA) by sponging chemokine receptor CXC chemokine receptor 4 (CXCR4).
ConclusionLncRNA HULC contributes to cholangiocarcinoma pathogenesis by targeting CXCR4 to affect cell proliferation and differentiation, lncRNA HULC might serve as a novel therapeutic target in cholangiocarcinoma
Key words:
Inflamation response; Oxidative stress; Competing endogenous RNA; Cholangiocarcinoma; Migration and invasion
Contributor Information
Hua Ye
Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
Bo He
Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
Jie Chen
Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
Chuanchao He
Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
Yibiao Ye
Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
Tao Chen
Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China