MicroRNA-221-3p promotes proliferation and invasion in non-small cell lung cancer via targeting Axin2 to regulate Wnt/β-catenin signaling pathway

Abstract

ObjectiveThe mortality rate of lung cancer ranks first in malignant tumors. Among them, non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer patients. In this study, we explore part of the mechanism of development and progression of NSCLC.Methods/ ResultsFirstly, there was an increase in microRNA-221-3p (miR-221-3p) expression and a decrease in Axin2 expression in NSCLC tissues using real-time reverse transcription polymerase chain reaction. Further studies showed that miR-221-3p inhibited the expression of Axin2, which negatively regulated the Wnt signaling pathway. With the method of inhibiting and overexpressing the expression of miR-221-3p and/or Axin2 respectively in NSCLC cell lines A549 and H1975, we found that inhibiting the expression of miR-221-3p leaded to a decrease in cell proliferation, migration and invasion, just like the results of overexpressing Axin2. Relatively speaking, overexpression of miR-221-3P in NSCLC cell lines showed the increase of proliferation as well as the decrease of apoptosis. Thus, we knew that miR-221-3p promoted the migration and invasion of NSCLC cells in vitro. What’s more, according to western blot and EdU assay, we demonstrated that overexpression of miR-221-3p inhibited the expression of Axin2 and subsequently activate classical Wnt/β-catenin signaling pathway. At last, a series of methods were used to identify that miR-221-3p inhibited Axin2 expression, increased cell proliferation, invasion and migration, and decreased cell apoptosis.ConclusionOur results suggest that miR-221-3p inhibits the expression of Axin2 and indirectly activates the typical Wnt/β-catenin signaling pathway, thus promoting tumor proliferation and invasion in NSCLC.

Serum Exosomes and Their miRNA Load—A Potential Biomarker of Lung Cancer

“…Among miR-221 targets is also CD117 , a known proto-oncogene that regulates cell survival, migration, and differentiation. Overexpression of miR-221 induces proliferation and migration of tumor cells as well as tumor angiogenesis via the Wnt/β-catenin signaling pathway and has been shown to promote the chemoresistance of lung cancer cells by activating the PTEN/Akt pathway [ 146 ]. miR-210 is also an important factor in the development of lung cancer, whose level increases in NSCLS tissues and is associated with a worse prognosis [ 147 ].…”