lncRNA PCBP1-AS1 Aggravates the Progression of Hepatocellular Carcinoma via Regulating PCBP1/PRL-3/AKT Pathway
Received 13 February 2020
Accepted for publication 10 June 2020
Published 6 July 2020 Volume 2020:12 Pages 5395—5408
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Yong Teng
Tianping Luo,1 Yuan Gao,1 Guangyan Zhangyuan,2 Xiaoliang Xu,3 Cailin Xue,1 Lei Jin,1 Wenjie Zhang,3 Chunfu Zhu,1 Beicheng Sun,3 Xihu Qin1
1Department of Hepatobiliary Surgery, The Affiliated Changzhou NO. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 213164, People’s Republic of China; 2Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, People’s Republic of China; 3Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province 210008, People’s Republic of China
Correspondence: Xihu Qin
Department of Hepatobiliary Surgery, The Affiliated Changzhou NO. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 213164, People’s Republic of China
Background: Hepatocellular carcinoma (HCC) is a very belligerent primary liver tumor with high metastatic potential. Aberrant expression of lncRNAs drives tumorous invasion and metastasis. Whether lncRNAs engage mechanisms of liver cancer metastasis remains largely unexplored.
Patients and Methods: We collected HCC tissues from the tumors and their adjacent normal samples in the Chinese population and analyzed the levels of lncRNAs by microarray analysis. The gain- and loss-of-function analysis demonstrated that PCBP1-AS1 accelerated tumorous growth and metastasis in vivo and in vitro. Moreover, we used RNA-pulldown assay to show that PCBP1-AS1 physically interacted with polyC-RNA-binding protein 1 (PCBP1); meanwhile, PCBP1-AS1 was indeed detected in RIP with the PCBP1 antibody. Mechanistically, we first explored the relationship between PCBP1‐AS1 and PCBP1 in HCC cell lines.
Results: Here we show that PCBP1-AS1, identified by microarray analysis on pre- and post-operative HCC plasma specimens, was highly expressed in human HCC, clinically verified as a prometastatic factor and markedly associated with poor prognosis in patients with hepatocellular carcinoma. PCBP1‐AS1 was negatively related with PCBP1 at the messenger RNA and protein expression levels. PCBP1-AS1 triggered PRL-3 and AKT in HCC tumor cells. Additionally, the double knockout of PCBP1 and PCBP1-AS1 abolished the PCBP1-AS1-induced PRL-3-AKT signalling pathway activation.
Conclusion: The upregulation of PCBP1-AS1 enhances proliferation and metastasis in HCC, thus regulating the PCBP1-PRL-3-AKT signalling pathway.
Keywords: hepatocellular carcinoma, long non-coding RNA, PCBP1-AS1, poly(C)-binding protein 1, AKT, hepatocarcinogenesis, metastasis
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