Exosomal miR-93 promotes proliferation and invasion in hepatocellular carcinoma by directly inhibiting TIMP2/TP53INP1/CDKN1A

Xiaofeng Xue; Xiaona Wang; Yubin Zhao; Rongkuan Hu; Lei Qin

doi:10.1016/j.bbrc.2018.05.208

Exosomal miR-93 promotes proliferation and invasion in hepatocellular carcinoma by directly inhibiting TIMP2/TP53INP1/CDKN1A

Biochem Biophys Res Commun. 2018 Aug 25;502(4):515-521. doi: 10.1016/j.bbrc.2018.05.208. Epub 2018 Jun 4.

Authors

Xiaofeng Xue¹, Xiaona Wang², Yubin Zhao³, Rongkuan Hu⁴, Lei Qin⁵

Affiliations

¹ Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: xfxue@suda.edu.cn.
² Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
³ College of Life Sciences, Shanxi Normal University, Xi'an, China.
⁴ Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science & Technology of China, Hefei, China. Electronic address: rkhu@mail.ustc.edu.cn.
⁵ Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: qinlei@suda.edu.cn.

PMID: 29859935
DOI: 10.1016/j.bbrc.2018.05.208

Abstract

Hepatocellular carcinoma (HCC) is a malignant cancer worldwide; lacking biomarkers for early prognostication contributes to its high lethality. Herein, we report a novel biomarker, exosome delivered miR-93, is up-regulated in HCC cell line media and serum samples of HCC patients. We measured the proliferation and invasion ability of HCC cell lines following exosomal miR-93 treatment. After prediction with online algorithms, we further confirmed that TP53INP1, TIMP2 and CDKN1A are direct targets of miR-93 by dual-luciferase reporter assay. In addition, the diagnostic value of exosomal miR-93 was evaluated by qPCR and ROC analysis. The significant correlation between serum exosomal miR-93 and clinical information including stage, tumor size were observed. Furthermore, the survival differences of HCC patients with high or low miR-93 were statistically significant using Kaplan-Meier analysis. In summary, our work identified exosomal miR-93 as a novel biomarker for both diagnosis and prognosis in HCC.

Keywords: Diagnosis; Exosome; Hepatocellular carcinoma; Prognosis; miR-93.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Carrier Proteins / antagonists & inhibitors*
Carrier Proteins / genetics
Carrier Proteins / metabolism
Cell Line, Tumor
Cell Proliferation / genetics
Cyclin-Dependent Kinase Inhibitor p21 / antagonists & inhibitors*
Cyclin-Dependent Kinase Inhibitor p21 / genetics
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Exosomes / genetics
Exosomes / metabolism
Female
Heat-Shock Proteins / antagonists & inhibitors*
Heat-Shock Proteins / genetics
Heat-Shock Proteins / metabolism
Hep G2 Cells
Humans
Liver Neoplasms / genetics*
Liver Neoplasms / metabolism
Male
MicroRNAs / genetics*
MicroRNAs / metabolism
Middle Aged
Neoplasm Invasiveness / genetics
Tissue Inhibitor of Metalloproteinase-2 / antagonists & inhibitors*
Tissue Inhibitor of Metalloproteinase-2 / genetics
Tissue Inhibitor of Metalloproteinase-2 / metabolism

Substances

Biomarkers, Tumor
CDKN1A protein, human
Carrier Proteins
Cyclin-Dependent Kinase Inhibitor p21
Heat-Shock Proteins
MIRN93 microRNA, human
MicroRNAs
TIMP2 protein, human
TP53INP1 protein, human
Tissue Inhibitor of Metalloproteinase-2