Effects of Dicer1 targeted by EBV-miR-BART6-5p on biological properties and radiosensitivity of nasopharyngeal carcinoma.

Abstract

OBJECTIVE:

To discuss the effects of Epstein-Barr virus (EBV)-encoded BamHI A rightward transcript (BART) microRNA (miR-BART6-5p) by targeting Dicer1 on biological properties and radiosensitivity of nasopharyngeal carcinoma (NPC).

METHODS:

NPC patients (n = 96) treated with radiotherapy were collected from Jan 2010 to Jan 2011. Real-time quantitative PCR (qRT-PCR) and western blot were carried out to measure the expression of miR-BART6-5p and Dicer1. Dual luciferase reporter gene assay verified that miR-BART6-5p targeted Dicer1. CCK8, wound-healing, Transwell and Annexin-FITC/PI were employed to evaluate the effects of Dicer1 mediated by miR-BART6-5p on biological characteristics of NPC cells. The radiosensitivity of miR-BART6-5p targeting Dicer1 was assessed in vitro and in vivo.

RESULTS:

Increased miR-BART6-5p and decreased Dicer1 were discovered in NPC patients, displaying a close association with T-stage, clinical stage, as well as Pre-DNA of NPC. While elevated Dicer1 and miR-BART6-5p down-regulation in NPC patients were found after effective radiotherapy. Both miR-BART6-5p and Dicer1 were prognostic factors of NPC. Down-regulation of miR-BART6-5p could enhance Dicer1 expression and inhibit NPC cell proliferation, invasion and migration with promoted apoptosis. Clone formation assay also showed miR-BART6-5p down-regulation reduced planting efficiency (PE), which further decreased with the increased dose of irradiation. Injection with miR-BART6-5p inhibitors in nude mice after 6-Gy irradiation contributed to the overexpression of Dicer1 and the inhibition of tumor growth.

CONCLUSIONS:

EBV-miR-BART6-5p may target Dicer1 to facilitate proliferation and metastasis of NPC cells and suppress apoptosis, thus being a new target for NPC therapy.

• Authors: Jing Tang, Zhao-Yang Liu, Yi Tang, Yan Wang
• Journal: Human & experimental toxicology (Hum Exp Toxicol) Vol. 40 Issue 6 Pg. 977-993 (Jun 2021) ISSN: 1477-0903 [Electronic] England
• PMID: 33305599 (Publication Type: Journal Article)

Chemical References

• MicroRNAs
• DEAD-box RNA Helicases

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Cell Line, Tumor (radiation effects)
• China
• DEAD-box RNA Helicases (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Herpesvirus 4, Human (genetics)
• Humans
• Male
• Mice
• Mice, Nude
• MicroRNAs (genetics)
• Middle Aged
• Nasopharyngeal Carcinoma (genetics, physiopathology, radiotherapy)
• Nasopharyngeal Neoplasms (genetics, physiopathology, radiotherapy)
• Radiation Tolerance (genetics)