MicroRNA-340 inhibits squamous cell carcinoma cell proliferation, migration and invasion by downregulating RhoA

J Dermatol Sci. 2018 Nov;92(2):197-206. doi: 10.1016/j.jdermsci.2018.09.003. Epub 2018 Sep 11.

Abstract

Background: MicroRNAs are reported to play an important role in tumor growth and metastasis, including squamous cell carcinoma (SCC). Accumulative evidence has revealed that dysregulated miR-340 expression contributed to the carcinogenesis and development of various cancers.

Objective: The aim of the current study was to investigate the role and the underlying mechanism of miR-340 in SCC cell proliferation, migration and invasion.

Methods: Quantitative real-time PCR was performed to examine the expression of miR-340 in SCC tissues and cell lines. The function of miR-340 in SCC was investigated through Cell Counting Kit-8, wound healing, transwell migration and invasion assays. Bioinformatics analysis, luciferase reporter assay, western blotting and immunohistochemical analysis were conducted to predict and confirm the target gene of miR-340.

Results: In the present study, we first found that miR-340 was significantly decreased in both SCC tissues and cell lines. Moreover, ectopic expression of miR-340 remarkably attenuated SCC cell proliferation, migration and invasion, whereas inhibition of endogenous miR-340 promoted SCC cell proliferation, migration and invasion in vitro. Our subsequent bioinformatics analysis and luciferase reporter assay showed that RhoA was a novel direct target of miR-340 in SCC cells, and the knockdown of RhoA expression rescued the effects of miR-340 inhibition on SCC cell proliferation, migration and invasion. More importantly, the expression of RhoA and miR-340 was negatively correlated in SCC tissues.

Conclusion: Our findings demonstrate the tumor suppressor role of miR-340 in SCC by directly regulating RhoA. Therefore, restoration of miR-340 expression can be a potential therapeutic approach for SCC treatment.

Keywords: Invasion; Proliferation; RhoA; Squamous cell carcinoma; miR-340.

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Signal Transduction / genetics
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • rhoA GTP-Binding Protein / genetics*
  • rhoA GTP-Binding Protein / metabolism

Substances

  • 3' Untranslated Regions
  • MIRN340 microRNA, human
  • MicroRNAs
  • RHOA protein, human
  • rhoA GTP-Binding Protein