MicroRNA‑122 regulates docetaxel resistance of prostate cancer cells by regulating <em>PKM2</em>

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.

MicroRNA-122 in human cancers: from mechanistic to clinical perspectives

“…This may be due to miR-122’s ability to regulate its target protein PKM2 by binding to the 3'-UTR. These results establish a causal relationship between miRNAs and PCa chemoresistance, suggesting that miRNA-122 targeting may represent a unique therapeutic approach for PCa chemoresistance [ 90 ].…”

The Mechanism of Warburg Effect-Induced Chemoresistance in Cancer

“…PKM2 can inhibit ROS accumulation and oxidative stress-induced apoptosis by binding to BCL2 protein on the mitochondrial membrane (100). Especially, miR-122 inhibits docetaxel resistance of prostate and hepatocellular cancer and 5-FU resistance of colon cancer by targeting PKM2 (106)(107)(108). Exosomes derived from chemoresistant cancer cells can transfer ciRS-122 across the cells and facilitate glycolysis to reduce oxaliplatin sensitivity in chemosensitive cells by inhibiting miR-122 and upregulating PKM2 in colorectal cancer (109).…”

Chimeric nanocomposites for the rapid and simple isolation of urinary extracellular vesicles

“…Urine specimens from 20 patients with PCa, 10 patients with BPH, and 10 healthy controls were analyzed. We profiled the expression levels of four EV‐derived miRNAs as a panel of prostate disease diagnosis (miR‐21, miR‐346 miR‐23a, and miR‐122‐5p (Foj et al., 2017 ; Jackson et al., 2014 ; Wang et al., 2019 ; Zhu et al., 2020 )) via their relative expression by using RT‐qPCR (Figure 8 ). The four EV‐derived miRNAs were found to be differentially expressed in both BPH and PCa compared to urine from healthy controls.…”