MiR-410 induces stemness by inhibiting Gsk3β but upregulating β-catenin in non-small cells lung cancer

Oncotarget. 2017 Feb 14;8(7):11356-11371. doi: 10.18632/oncotarget.14529.

Abstract

Our previous research indicated miR-410 played a critical role in promoting the tumorigenesis and development of NSCLC (non-small cells lung cancer). MiR-410 has been recently reported to be crucial for development and differentiation of embryonic stem cells. But it remains elusive whether miR-410 stimulates the stemness of cancer until now. Herein, we identify miR-410 induces the stemness and is associated with the progression of NSCLC. We demonstrate miR-410 increases the levels of stem cells marker Sox2, Oct4, Nanog, CXCR4 as well as lung cancer stem cells surface marker CD44 and CD166. MiR-410 promotes stem cells-like properties such as proliferation, sphere formation, metastasis and chemoresistance. Moreover, Gsk3β is directly targeted and post-transcriptionally downregulated by miR-410. Also, the expression levels of miR-410 and Gsk3β may be correlated to clinicopathological differentiation in NSCLC tumor specimens. Additionally, we demonstrate miR-410 induces stemness through inhibiting Gsk3β but increasing Sox2, Oct4, Nanog and CXCR4, which binds to β-catenin signaling. In conclusion, our findings identify the miR-410/Gsk3β/β-catenin signaling axis is a novel molecular circuit in inducing stemness of NSCLC.

Keywords: Wnt/β-catenin; miR-410; non-small cells lung cancer; stemness.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic / genetics*
  • Glycogen Synthase Kinase 3 beta / biosynthesis*
  • Glycogen Synthase Kinase 3 beta / genetics
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / physiology
  • Up-Regulation
  • beta Catenin / biosynthesis*
  • beta Catenin / genetics

Substances

  • CTNNB1 protein, human
  • MIRN410 microRNA, human
  • MicroRNAs
  • beta Catenin
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta