Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

16 July 2016 : Laboratory Research  

HBX Protein-Induced Downregulation of microRNA-18a is Responsible for Upregulation of Connective Tissue Growth Factor in HBV Infection-Associated Hepatocarcinoma

Xiaomin LiuBCDE, Yingjian ZhangABCDFG, Ping WangCD, Hongyun WangCD, Huanhuan SuCD, Xin ZhouCD, Lamei ZhangCD

DOI: 10.12659/MSM.895943

Med Sci Monit 2016; 22:2492-2500

Abstract

BACKGROUND: This study was designed to improve our understanding of the role of miR-18a and its target (connective tissue growth factor (CTGF), which are mediators in HBX-induced hepatocellular carcinoma (HCC).

MATERIAL AND METHODS: We first investigated the expression of several candidate microRNAs (miRNAs) reported to have been aberrantly expressed between HepG2 and HepG2.2.15, which is characterized by stable HBV infection, while the CTGF is identified as a target of miR-18a. Furthermore, the expression of CTGF evaluated in HepG2 was transfected with HBX, while the HepG2.2.15 was transfected with miR-18a and CTGF siRNA. We examined the cell cycle at the same time.

RESULTS: We found that the expression of miR-18a was abnormally reduced in the HBV-positive HCC tissue samples compared with HBV-negative HCC samples. Through the use of a luciferase reporter system, we also identified CTGF 3’UTR (1046–1052 bp) as the exact binding site for miR-18a. We also observed a clear increase in CTGF mRNA and protein expression levels in HBV-positive HCC human tissue samples in comparison with the HBV-negative controls, indicating a possible negatively associated relationship between miR-18a and CTGF. Furthermore, we investigated the effect of HBX overexpression on miR-18a and CTGF, as well as the viability and cell cycle status of HepG2 cells. In addition, we found that HBX introduction downregulated miR-18a, upregulated CTGF, elevated the viability, and promoted cell cycle progression. We transfected HepG2.2.15 with miR-18a mimics and CTGF siRNA, finding that upregulated miR-18a and downregulated CTGF suppress the viability and cause cell cycle arrest.

CONCLUSIONS: Our study shows the role of the CTGF gene as a target of miR-18a, and identifies the function of HBV/HBX/miR-18a/CTGF as a key signaling pathway mediating HBV infection-induced HCC.

Keywords: Case-Control Studies, Carcinoma, Hepatocellular - virology, Cell Cycle Checkpoints - genetics, Connective Tissue Growth Factor - metabolism, Hepatitis B virus - metabolism, Hepatitis B, Chronic - virology, Liver Neoplasms - virology, RNA, Messenger - metabolism, Trans-Activators - metabolism

Add Comment 0 Comments

956 3

Editorial

01 December 2023 : Editorial  

Editorial: Outbreaks of Post-Pandemic Childhood Pneumonia and the Re-Emergence of Endemic Respiratory Infections

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.943312

Med Sci Monit 2023; 29:e943312

In Press

01 Dec 2023 : Clinical Research  

Risk Factors and Clinical Outcomes of COVID-19 Infection in Multiple Sclerosis Patients: A Retrospective St...

Med Sci Monit In Press; DOI:  

30 Nov 2023 : Review article  

Decoding the Neurological Sequelae of General Anesthesia: A Review

Med Sci Monit In Press; DOI:  

30 Nov 2023 : Clinical Research  

Enhanced Pain Relief and Muscle Growth in Individuals with Low Back Instability: The Impact of Blood Flow R...

Med Sci Monit In Press; DOI:  

29 Nov 2023 : Clinical Research  

Comparative Analysis of Intramedullary Nail versus Plate Fixation for Fibula Fracture in Supination Externa...

Med Sci Monit In Press; DOI:  

Most Viewed Current Articles

13 Nov 2021 : Clinical Research  

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...

DOI :10.12659/MSM.932788

Med Sci Monit 2021; 27:e932788

0:00

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

0:00

14 Dec 2022 : Clinical Research  

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750