MicroRNA-122 regulates docetaxel resistance of prostate cancer cells by regulating PKM2.

Abstract

Prostate cancer (PCa), an epithelial malignancy that occurs in the prostate, is the second leading cause of cancer death worldwide. MicroRNAs (miRs/miRNAs) are reported to have important applications in the field of cancer diagnosis and treatment. The present study aimed to investigate the function of miRNA-122 in the chemoresistance of PCa cells and the underlying mechanism. Significantly decreased miR-122 and increased pyruvate kinase (PKM2) levels were observed in docetaxel-resistant PCa cells, and PKM2 was negatively correlated with miR-122. MiR-122 mimic transfection in docetaxel-resistant LNCaP cells significantly inhibited cell proliferation, promoted apoptosis and decreased glucose uptake and lactate production, which was counteracted by PKM2 overexpression. Inhibition of miR-122 in LNCaP cells had an opposite effect to miR-122 mimic transfection. In addition, miR-122 mimic transfection significantly increased the sensitivity of docetaxel-resistant LNCaP cells to docetaxel, while inhibition of miR-122 significantly decreased the sensitivity of LNCaP cells to docetaxel. Luciferase reporter assays showed that miR-122 regulated PKM2 expression by binding to the 3'-untranslated region of PKM2. The results suggest that upregulation of miR-122 could enhance docetaxel sensitivity, inhibit cell proliferation and promote apoptosis in PCa cells,possibly through the downregulation of its target protein PKM2.