Exosomal miR-638 Inhibits Hepatocellular Carcinoma Progression by Targeting SP1
Authors Yang J, Li B, Zhao S, Du H, Du Y
Received 9 March 2020
Accepted for publication 15 June 2020
Published 7 July 2020 Volume 2020:13 Pages 6709—6720
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Leo Jen-Liang Su
This paper has been retracted.
Jing Yang, 1 Bo Li, 1 Shuo Zhao, 2 Hongyu Du, 1 Yaming Du 3
1Department of Pathology, Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of China; 2Department of Nursing, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of China; 3Department of Vascular Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of China
Correspondence: Yaming Du Email firstname.lastname@example.org
Purpose: Exosomal microRNAs (miRNAs) play essential roles in the development of hepatocellular carcinoma (HCC). Nevertheless, the role and mechanism of exosomal miR-638 in HCC development remain largely unknown.
Methods: Exosomes were isolated and confirmed via transmission electron microscopy and western blot. The abundances of miR-638 and specificity protein 1 (SP1) were measured via quantitative reverse transcription polymerase chain reaction or western blot. Cell proliferation was investigated by Cell Counting Kit-8, colony formation assay, apoptosis, cell cycle distribution and related protein expression. Cell migration and invasion were detected via transwell assay and western blot. Co-culture experiment was performed to assess exosome transfer from HCC cells to endothelial cells. The target correlation between miR-638 and SP1 was analyzed via dual-luciferase reporter and RNA immunoprecipitation assays. The subcutaneous xenograft experiment was conducted to test the function of miR-638 in vivo.
Results: The miR-638 level declined in exosomes from serum or HCC cell medium. miR-638 overexpression repressed HCC cell proliferation by decreasing viability and colony formation and inducing apoptosis and cell cycle arrest at G1 phase, and decreased abilities of migration and invasion. Exosomal miR-638 from HCC cells could transfer to human umbilical vein endothelial cells (HUVECs) and suppress HUVEC proliferation, migration and invasion. SP1 was a target of miR-638 and overexpression of SP1 reversed the effect of miR-638 on HCC cells. Overexpression of miR-638 reduced xenograft tumor growth via decreasing SP1.
Conclusion: Exosomal miR-638 inhibited HCC tumorigenesis by targeting SP1. This study indicated the potential clinical implications of miR-638 in HCC.
Keywords: hepatocellular carcinoma, exosome, miR-638, SP1
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