scholarly journals Oncogenic Secretory Clusterin: A Promising Therapeutic Target for Hepatocellular Carcinoma

Author(s):  
Min Yao ◽  
Wenjie Zheng ◽  
Li Wang ◽  
Miao Fang ◽  
Dengfu Yao ◽  
...  
2017 ◽  
Vol 46 (7) ◽  
pp. 1301-1313 ◽  
Author(s):  
Parvin Zamani ◽  
Maryam Matbou Riahi ◽  
Amir Abbas Momtazi-Borojeni ◽  
Khadijeh Jamialahmadi

2017 ◽  
Vol 43 (5) ◽  
pp. 1926-1938 ◽  
Author(s):  
Jia Xiao ◽  
Yi Lv ◽  
Fujun Jin ◽  
Yingxia Liu ◽  
Yi Ma ◽  
...  

Background/Aims: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third leading cause of cancer-related death. Critical roles for long non-coding RNAs (lncRNAs) have recently been demonstrated for a variety of cancers, including hepatocellular carcinoma. However, the effect and mechanism of lncRNAs in HCC tumorigenesis and chemoresistance have not been extensively characterized. Methods: In the current study, we have identified a HCC-expressed lncRNA termed as HANR (HCC associated long non-coding RNA). We identified HANR by microarray analysis and validated its up-regulated expression by quantitative PCR. RNA pull-down and pathway analyses were conducted to evaluate physical and functional interactions with HANR. In vivo experiments were performed to assess tumorigenesis and increase of chemoresistance. In addition, the HANR expression in HCC specimens was detected by FISH. Xenograft and orthotopic mice model was constructed to observe the effect of HANR on tumorigenesis and chemoresistance in vivo. Results: HANR was demonstrated to be up-regulated in HCC patients and HCC cell lines. Increased HANR expression in HCC predicted short survival of patients. Knock-down of HANR markedly retarded cell proliferation, suppressed HCC xenograft/orthotopic tumor growth, induced apoptosis and enhanced chemosensitivity to doxorubicin, while over-expression of HANR showed the opposite effects. It was found that HANR bind to GSKIP for regulating the phosphorylation of GSK3β in HCC. Conclusion: Our results demonstrate that HANR contributes to the development of HCC and is a promising therapeutic target for chemosensitization of HCC cells to doxorubicin, which may represent a promising therapeutic target in the future.


2021 ◽  
Vol 8 ◽  
Author(s):  
Yanjiao Ou ◽  
Yong Deng ◽  
Hong Wang ◽  
Qingyi Zhang ◽  
Huan Luo ◽  
...  

Objective: Increasing evidence highlights antisense long non-coding RNAs (lncRNAs) as promising therapeutic targets for cancers. Herein, this study focused on the clinical implications and functions of a novel antisense lncRNA PRKAG2-AS1 in hepatocellular carcinoma (HCC).Methods: PRKAG2-AS1 expression was examined in a cohort of 138 HCC patients by RT-qPCR. Overall survival (OS) and disease-free survival (DFS) analyses were presented based on PRKAG2-AS1 expression, followed by ROCs. After silencing PRKAG2-AS1, cell proliferation was assessed via CCK-8, colony formation and EdU staining assays. Migrated and invasive capacities were assessed by wound healing and transwell assays. The relationships between PRKAG2-AS1, miR-502-3p and BICD2 were validated by luciferase reporter, RIP and RNA pull-down assays. The expression and prognostic value of BICD2 were analyzed in TCGA database.Results: PRKAG2-AS1 was up-regulated in HCC than normal tissue specimens. High PRKAG2-AS1 expression was indicative of poorer OS and DFS time. Area under the curves (AUCs) for OS and DFS were 0.8653 and 0.7891, suggesting the well predictive efficacy of PRKAG2-AS1 expression. Targeting PRKAG2-AS1 distinctly inhibited proliferation, migration, and invasion in HCC cells. PRKAG2-AS1 was mainly expressed in cytoplasm of HCC cells. PRKAG2-AS1 may directly bind to the sites of miR-502-3p. Up-regulation of BICD2 was found in HCC tissues and associated with unfavorable prognosis. BICD2 was confirmed to be a downstream target of miR-502-3p. PRKAG2-AS1 could regulate miR-502-3p/BICD2 axis.Conclusion: Our findings identified a novel lncRNA PRKAG2-AS1 that was associated with clinical implications and malignant behaviors. Thus, PRKAG2-AS1 could become a promising therapeutic target.


DNA Repair ◽  
2016 ◽  
Vol 47 ◽  
pp. 12-20 ◽  
Author(s):  
Rosa M. Pascale ◽  
Christy Joseph ◽  
Gavinella Latte ◽  
Matthias Evert ◽  
Francesco Feo ◽  
...  

2019 ◽  
Author(s):  
Silvia Scaricamazza ◽  
Illari Salvatori ◽  
Giacomo Giacovazzo ◽  
Jean Philippe Loeffler ◽  
Frederique Renè ◽  
...  

2019 ◽  
Author(s):  
Yu-Han Yang ◽  
Juan Wang ◽  
Hang Li ◽  
An-Qian Lu ◽  
An-Na Chen ◽  
...  

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