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miR-181a decelerates proliferation in cutaneous squamous cell carcinoma by targeting the proto-oncogene KRAS

Johannes Neu1, Piotr Jan Dziunycz1, Andreas Dzung1

  • 1Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.

Plos One
|September 21, 2017
PubMed

Insights

MicroRNA-181a (miR-181a) acts as a tumor suppressor in cutaneous squamous cell carcinoma (SCC). Lowering miR-181a promotes cancer growth, while increasing it inhibits tumor formation by targeting KRAS.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Cutaneous squamous cell carcinoma (SCC) is a prevalent human skin cancer with rising incidence.
  • MicroRNAs (miRNAs) are recognized as critical regulators in cancer progression.
  • Dysregulation of specific miRNAs, like miR-181a, is implicated in SCC development.

Purpose of the Study:

  • To investigate the role of microRNA-181a (miR-181a) in cutaneous squamous cell carcinoma (SCC).
  • To explore the therapeutic potential of modulating miR-181a levels in SCC.
  • To elucidate the molecular mechanisms underlying miR-181a's function in SCC.

Main Methods:

  • Quantitative analysis of miR-181a expression in SCC tissues versus normal skin.
  • In vitro studies using primary keratinocytes and SCC cell lines to assess proliferation and apoptosis.
  • In vivo experiments in mouse models to evaluate tumor growth and therapeutic effects.
  • Analysis of KRAS (proto-oncogene) and MAPK pathway (phospho-ERK) modulation by miR-181a.

Main Results:

  • miR-181a was found at low levels in SCC compared to normal skin.
  • Downregulation of miR-181a increased keratinocyte proliferation and tumor-like growth in vivo.
  • Overexpression of miR-181a reduced SCC cell proliferation, induced apoptosis, and significantly inhibited tumor formation in mice.
  • miR-181a directly targeted KRAS, and its modulation inversely affected KRAS mRNA and protein levels.
  • KRAS knockdown mimicked miR-181a's anti-proliferative effects, and phospho-ERK levels correlated with KRAS, indicating MAPK pathway involvement.

Conclusions:

  • miR-181a functions as a significant tumor suppressor in cutaneous squamous cell carcinoma.
  • The tumor suppressive role of miR-181a is mediated through the targeting of KRAS and subsequent modulation of the MAPK signaling pathway.
  • miR-181a may be a promising candidate for novel miRNA-based therapeutic strategies against SCC.

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