BACKGROUND: Replication protein A (RPA) 3 is a subunit of the RPA protein complex, which functions in multiple processes of DNA metabolism. Dysregulation of RPA1 and RPA2 has been implicated in tumor progression in several cancer types. However, the function of RPA3 in hepatocellular carcinoma (HCC) tumorigenesis has not been elucidated. METHOD: In this study, we investigated the function of RPA3 in HCC development by stably knocking down its expression using short hairpin RNA (shRNA) in HepG2 cell line, followed by cell proliferation, colony formation, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumor-promoting properties of RPA3. RESULTS: Downregulation of RPA3-inhibited cell proliferation, colony formation, soft agar growth as well as invasion in HepG2 cells were observed. Stable knockdown of RPA3 significantly inhibited tumor growth in the xenograft mouse model. In addition, qRT-PCR analysis revealed that RPA3 was upregulated in human HCC tissues compared with matched noncancerous adjacent tissues (NATs). High expression of RPA3 was associated with poor overall survival and disease-free survival. CONCLUSION: Elevated expression of RPA3 promotes tumor progression in HCC cells. RPA3 is upregulated in HCC tissues and high expression of RPA3 is associated with poorer patient survival. Therefore, this protein may represent a novel therapeutic target for intervention of HCC and prognostic biomarker for patient survival.
BACKGROUND:Replication protein A (RPA) 3 is a subunit of the RPA protein complex, which functions in multiple processes of DNA metabolism. Dysregulation of RPA1 and RPA2 has been implicated in tumor progression in several cancer types. However, the function of RPA3 in hepatocellular carcinoma (HCC) tumorigenesis has not been elucidated. METHOD: In this study, we investigated the function of RPA3 in HCC development by stably knocking down its expression using short hairpin RNA (shRNA) in HepG2 cell line, followed by cell proliferation, colony formation, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumor-promoting properties of RPA3. RESULTS: Downregulation of RPA3-inhibited cell proliferation, colony formation, soft agar growth as well as invasion in HepG2 cells were observed. Stable knockdown of RPA3 significantly inhibited tumor growth in the xenograft mouse model. In addition, qRT-PCR analysis revealed that RPA3 was upregulated in human HCC tissues compared with matched noncancerous adjacent tissues (NATs). High expression of RPA3 was associated with poor overall survival and disease-free survival. CONCLUSION: Elevated expression of RPA3 promotes tumor progression in HCC cells. RPA3 is upregulated in HCC tissues and high expression of RPA3 is associated with poorer patient survival. Therefore, this protein may represent a novel therapeutic target for intervention of HCC and prognostic biomarker for patient survival.
Authors: Yun-Miao Guo; Jie-Rong Chen; Yan-Chun Feng; Melvin L K Chua; Yanni Zeng; Edwin Pun Hui; Allen K C Chan; Lin-Quan Tang; Lin Wang; Qian Cui; Hui-Qiong Han; Chun-Ling Luo; Guo-Wang Lin; Yan Liang; Yang Liu; Zhong-Lian He; Yu-Xiang Liu; Pan-Pan Wei; Chu-Jun Liu; Wan Peng; Bo-Wei Han; Xiao-Yu Zuo; Enya H W Ong; Eugenia L L Yeo; Kar Perng Low; Gek San Tan; Tony K H Lim; Jacqueline S G Hwang; Bo Li; Qi-Sheng Feng; Xiaojun Xia; Yun-Fei Xia; Josephine Ko; Wei Dai; Maria L Lung; Anthony T C Chan; Dennis Y M Lo; Mu-Sheng Zeng; Hai-Qiang Mai; Jianjun Liu; Yi-Xin Zeng; Jin-Xin Bei Journal: Adv Sci (Weinh) Date: 2020-03-20 Impact factor: 16.806
Authors: Dai Zhang; Si Yang; Yiche Li; Jia Yao; Jian Ruan; Yi Zheng; Yujiao Deng; Na Li; Bajin Wei; Ying Wu; Zhen Zhai; Jun Lyu; Zhijun Dai Journal: JAMA Netw Open Date: 2020-10-01