Overexpression of miR-4443 promotes the resistance of non-small cell lung cancer cells to epirubicin by targeting INPP4A and regulating the activation of JAK2/STAT3 pathway

Die Pharmazie
Weiguo ZhangJunli Fan

Abstract

We aimed to elucidate the roles and regulatory mechanism of miR-4443 in regulating the resistance of non-small cell lung cancer (NSCLC) cells to epirubicin (EPI). Fifty-four advanced NSCLC patients were classified as ''insensitive'' or ''sensitive'' according to patient's responses following EPI-based chemotherapy and then the expression of miR-4443 was determined. The EPI-resistant H1299 cells were collected and transfected with miR-4443 mimics, whereas parental H1299 cells were transfected with miR-4443 inhibitors. The inhibition of growth (IC50), cell cycle or apoptosis of different transfected groups were investigated. Additionally, the potential target of miR-3188 was identified and verified by luciferase reporter assay. Besides, the regulatory relationship between miR-3188 and JAK2/STAT3 pathway was explored. miR-4443 was highly expressed in insensitive NSCLC patients to EPT-based chemotherapy and EPI-resistant H1299 cells. Inhibition of miR-4443 increased the sensitivity of EPI-resistant H1299 cells to EPI by decreasing IC50 of EPI, inducing cell apoptosis and G0/G1 cell cycle arrest, while overexpression of miR-4443 promoted the resistance of parental H1299 cells to EPI. Furthermore, inositol polyphosphate 4-phosphatase...Continue Reading

Citations

Feb 16, 2019·Scientific Reports·Chikako RaganThomas Preiss

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