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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
DOI https://doi.org/10.2147/OTT.S152611
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
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