Journal
ONCOTARGET
Volume 8, Issue 7, Pages 11356-11371Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.14529
Keywords
miR-410; stemness; Wnt/beta-catenin; non-small cells lung cancer
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Funding
- National 973 Plan Project [2010CB529906]
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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, Gsk3 beta is directly targeted and post-transcriptionally downregulated by miR-410. Also, the expression levels of miR-410 and Gsk3 beta may be correlated to clinicopathological differentiation in NSCLC tumor specimens. Additionally, we demonstrate miR-410 induces stemness through inhibiting Gsk3 beta but increasing Sox2, Oct4, Nanog and CXCR4, which binds to beta-catenin signaling. In conclusion, our findings identify the miR-410/Gsk3 beta/beta-catenin signaling axis is a novel molecular circuit in inducing stemness of NSCLC.
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