MicroRNA Signatures for circulating CD133-positive cells in hepatocellular carcinoma with HCV infection

Abdel-Rahman N Zekri; Enas Reda El-Sisi; Amira Salah El-Din Youssef; Mahmoud M Kamel; Auhood Nassar; Ola Sayed Ahmed; Mohamed El Kassas; Ahmed Barakat Barakat; Alaa Ismail Abd El-Motaleb; Abeer A Bahnassy

doi:10.1371/journal.pone.0193709

MicroRNA Signatures for circulating CD133-positive cells in hepatocellular carcinoma with HCV infection

PLoS One. 2018 Mar 13;13(3):e0193709. doi: 10.1371/journal.pone.0193709. eCollection 2018.

Affiliations

¹ Molecular Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
² Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
³ Photobiology and Molecular Biology Department, Laser Institute for Research and Applications (LIRA), Beni-Suef University, Beni Suef, Egypt.
⁴ Endemic Medicine Department, Faculty of Medicine, Helwan University, Helwan, Egypt.
⁵ Microbiology Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
⁶ Surgery Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
⁷ Tissue Culture and Cytogenetics Unit, Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

Abstract

Aim: Molecular characterization of the CD133+ stem cells associated with hepatocarinogensis through identifying the expression patterns of specific microRNAs (miRNAs).

Methods: We investigated the expression pattern of 13 miRNAs in purified CD133+ cells separated from the peripheral blood of healthy volunteers, chronic hepatitis C (CHC), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) patients a long with bone marrow samples from the healthy volunteers and the LC patients using custom miScript miRNA PCR array.

Results: The differential expression of the 13 studied miRNAs in CD133+ cells separated from the HCC patients' peripheral blood compared to the controls revealed that miR-602, miR-181b, miR-101, miR-122, miR-192, miR-125a-5p, and miR-221 were significantly up regulated (fold change = 1.8, 1.7, 2, 5.4, 1.6, 2.9 & 1.5 P value = 0.039, 0.0019, 0.0013, 0.0370, 00024, 0.000044 &0.000007 respectively). As for the HCC group compared to the CHC group; miR-602, miR-122, miR-181b, miR-125a-5p, and miR-192 were significantly up regulated (fold change = 13, 3.1, 2.8, 1.6 & 1.56, P value = 0.01, 0.001, 0.000004, 0.002 & 0.007 respectively). Upon comparing the HCC group to the LC group; miR-199a-3p, miR-192, miR-122, miR-181b, miR-224, miR-125a-5p, and miR-885-5p were significantly up regulated (fold change = 5, 6.7, 2.3, 3, 2.5, 4.2 & 39.5 P value = 0.001025, 0.000024, 0.000472, 0.000278, 0.000004, 0.000075 & 0.0000001 respectively) whereas miR-22 was significantly down regulated (fold change = 0.57 P value = 0.00002). Only, miR-192, miR-122, miR-181b and miR-125a-5p were significant common miRNAs in CD133+ cells of the HCC group compared to the other non-malignant groups.

Conclusion: We identified a miRNA panel comprised of four miRNAs (miR-192, miR-122, miR-181b and miR-125a-5p) that may serve as a molecular tool for characterization of the CD133+ cells associated with different stages of hepatocarinogensis. This panel may aid in developing a new target therapy specific for those CD133+ cells.

Publication types

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

MeSH terms

AC133 Antigen / metabolism*
Adult
Aged
Aged, 80 and over
Bone Marrow / metabolism
Carcinoma, Hepatocellular / blood
Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / pathology
Carcinoma, Hepatocellular / virology
Female
Gene Expression Profiling*
Gene Expression Regulation, Neoplastic
HIV / physiology*
Humans
Liver Neoplasms / blood
Liver Neoplasms / genetics*
Liver Neoplasms / pathology
Liver Neoplasms / virology
Male
MicroRNAs / genetics*
Middle Aged
Neoplastic Cells, Circulating / metabolism*
Retrospective Studies

Substances

AC133 Antigen
MicroRNAs

Associated data

figshare/5923705

Grants and funding

This work was supported by Science and Technology Development Fund #5193 to ARNZ and Egypt National Cancer Institute. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.