miR-106b-5p promotes stem cell-like properties of hepatocellular carcinoma cells by targeting PTEN via PI3K/Akt pathway
Authors Shi DM, Bian XY, Qin CD, Wu WZ
Received 26 September 2017
Accepted for publication 15 November 2017
Published 26 January 2018 Volume 2018:11 Pages 571—585
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 4
Editor who approved publication: Dr Ingrid Espinoza
Dong-Min Shi,* Xin-Yu Bian,* Cheng-Dong Qin,* Wei-Zhong Wu
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People’s Republic of China
*These authors contributed equally to this work
Background: The miRNA miR-106b-5p has been previously reported to be increased in hepatocellular carcinoma (HCC) tissues compared to cirrhotic tissues. The purpose of this study was to detect its expression in HCC cell lines with distinct metastatic potentials and to explore the molecular mechanisms underlying HCC stemness and migration.
Methods: miR-106b-5p expression was studied in HCC tissues and cell lines. In vitro cancer stem cell (CSC)-like properties, cell migration and invasion were compared between HCC cell lines with upregulation or downregulation of miR-106b-5p. In vivo tail vein injection models were established to evaluate the role of miR-106b-5p in lung metastasis. Bioinformatics programs, luciferase reporter assay and rescue experiments were used to validate the downstream targets of miR-106b-5p. The relationship between the expression of the targeted gene and clinicopathological parameters was also analyzed.
Results: miR-106b-5p expression was higher in HCC tissues and cell lines than that in non-tumor tissues and hepatocyte Chang liver, respectively. Upregulation of miR-106b-5p exhibited a promoting role in CSC properties, cell migration and activation of phosphatidylinositol-3 kinase (PI3K)/Akt signaling in vitro, as well as in lung metastasis in vivo. However, downregulation of miR-106b-5p exhibited the opposite effect. Furthermore, PTEN was verified as a direct target of miR-106b-5p. Upon clinicopathological analysis, lower level of PTEN was significantly associated with more aggressive characteristics. Patients with high PTEN expression had longer overall survival and disease-free survival.
Conclusion: miR-106b-5p promotes HCC stemness maintenance and metastasis by targeting PTEN via PI3K/Akt pathway. Inhibition of miR-106b-5p might be effective therapeutic strategies to treat advanced HCC.
Keywords: HCC, miRNAs, CSC-like properties, metastasis
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