miR-17-5p drives G2/M-phase accumulation by directly targeting CCNG2 and is related to recurrence of head and neck squamous cell carcinoma

BMC Cancer. 2021 Oct 2;21(1):1074. doi: 10.1186/s12885-021-08812-6.

Abstract

Background: The human miR-17-92 polycistron is the first reported and most well-studied onco-miRNA with a cluster of seven miRNAs. miR-17-5p, a member of the miR-17-92 family, plays an important role in tumor cell proliferation, apoptosis, migration and invasion. However, few studies have shown the role of miR-17-5p in the cell cycle of head and neck squamous cell carcinoma (HNSCC).

Methods: RT-qPCR was used to detect miR-17-5p expression levels in 64 HNSCC tissues and 5 cell lines. The relationship between the expression of miR-17-5p in the tissues and the clinical characteristics of the patients was analyzed. HNSCC cells were transfected with an miR-17-5p mimic or inhibitor to evaluate cell cycle distribution by flow cytometry. Cell cycle distribution of cells transfected with target gene was evaluated using flow cytometry. Dual-luciferase reporter assay was used to detect the regulatory effect of miR-17-5p on target gene expression.

Results: In the present study, we found that miR-17-5p expression in HNSCC tissues and cell lines was remarkably increased, and miR-17-5p is related to recurrence in HNSCC patients. Silencing miR-17-5p blocked HNSCC cells in G2/M phase, whereas its overexpression propelled cell cycle progression. More importantly, we verified that miR-17-5p negatively regulated CCNG2 mRNA and protein expression by directly targeting its 3'UTR.

Conclusion: These findings suggest that miR-17-5p might act as a tumor promoter and prognostic factor for recurrence in HNSCC patients.

Keywords: CCNG2; Cell cycle; HNSCC; Recurrence; miR-17-5p.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Apoptosis / genetics
  • Area Under Curve
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cyclin G2 / genetics
  • Cyclin G2 / metabolism*
  • Down-Regulation
  • Female
  • G2 Phase Cell Cycle Checkpoints*
  • Gene Silencing
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism*
  • Humans
  • Luciferases / metabolism
  • M Phase Cell Cycle Checkpoints*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / metabolism
  • RNA, Messenger / metabolism
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / metabolism*
  • Transfection
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • CCNG2 protein, human
  • Cyclin G2
  • MIRN17 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Luciferases