MicroRNA-26a inhibits proliferation and tumorigenesis via targeting CKS2 in laryngeal squamous cell carcinoma

Clin Exp Pharmacol Physiol. 2018 May;45(5):444-451. doi: 10.1111/1440-1681.12890. Epub 2018 Jan 8.

Abstract

Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck cancers, with high mortality and incidence. MicroRNA-26a (miR-26a) is involved in the development and progression of several tumours. However, the roles of miR-26a and its target CKS2 in LSCC progression are not yet clear. The mRNA and protein expression was determined using RT-PCR and Western blotting assay, respectively. Cell proliferation was detected using a Cell Counting kit-8 assay (CCK-8). Transwell assay was used to evaluate cell migration and invasion. Dual-luciferase reporter assay was applied to determine the relationship between miR-26a and CKS2. In addition, a tumour xenograft model in nude mice was established to further determine the effects of miR-26a on tumourigenesis. In this study, we found that miR-26a level was down-regulated in LSCC tissues and cell lines, while CKS2 expression was increased. Cell proliferation, migration, invasion and the expression of MMP2 and MMP9 was suppressed by miR-26a overexpression, but enhanced by inhibition of miR-26a. Dual-luciferase reporter assay demonstrated that CKS2 is a direct target of miR-26a in AMC-HN-8 cells. Overexpression of miR-26a caused a significant reduction in CKS2 expression, and reinforced expression of CKS2 abolished the tumour-suppressive function of miR-26a. Moreover, miR-26a inhibited tumour growth in vivo. Taken together, miR-26a inhibited proliferation and tumourigenesis of LSCC via targeting CKS2 in vitro and in vivo.

Keywords: cyclin-dependent kinases regulatory subunit 2; laryngeal squamous cell carcinoma; microRNA-26a; migration; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CDC2-CDC28 Kinases / genetics*
  • Carcinogenesis / genetics*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology*
  • Carrier Proteins / genetics*
  • Cell Cycle Proteins / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Laryngeal Neoplasms / genetics
  • Laryngeal Neoplasms / pathology*
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • MIRN26A microRNA, human
  • MicroRNAs
  • CDC2-CDC28 Kinases
  • CKS2 protein, human