miR‐137 inhibits proliferation of melanoma cells by targeting PAK2

Abstract

Ferroptosis is a regulated form of cell death driven by small molecules or conditions that induce lipid-based reactive oxygen species (ROS) accumulation. This form of iron-dependent cell death is morphologically and genetically distinct from apoptosis, necroptosis, and autophagy. miRNAs are known to play crucial roles in diverse fundamental biological processes. However, to date no study has reported miRNA-mediated regulation of ferroptosis. Here we show that miR-137 negatively regulates ferroptosis by directly targeting glutamine transporter SLC1A5 in melanoma cells. Ectopic expression of miR-137 suppressed SLC1A5, resulting in decreased glutamine uptake and malondialdehyde (MDA) accumulation. Meanwhile, antagomir-mediated inactivation of endogenous miR-137 increased the sensitivity of melanoma cells to erastin-and RSL3-induced ferroptosis. Importantly, knockdown of miR-137 increased the antitumor activity of erastin by enhancing ferroptosis both in vitro and in vivo. Collectively, these data indicate that miR-137 plays a novel and indispensable role in ferroptosis by inhibiting glutaminolysis and suggest a potential therapeutic approach for melanoma.

MicroRNA‐7‐5p induces cell growth inhibition, cell cycle arrest and apoptosis by targeting PAK2 in non‐small cell lung cancer

“…It has been shown that PAK2 regulates actin cytoskeleton remodeling, motility, differentiation, and attachment in numerous cellular contexts, including cancer cells [14,16,17]. Similar expression profiles of PAK2 have been found in ovarian cancer cell lines and normal ovarian epithelial cells, and overexpression of PAK2 has been reported in melanoma cells [18,19]. PAK2 deficiency strongly inhibited the migration and invasion of ovarian cancer cells, but had no effect on cell viability and apoptosis [18].…”

“…Regulation of PAK2 by miR-7-5p was confirmed by in vitro transfection experiment in A549 and H1299 and by strongly suggesting the direct binding of the miR-7-5p 5 0 seed to the PAK2 30-UTR with the use of dual-luciferase reporter assay. Overexpression or amplification of PAK2 has been shown in gastric cancer and melanoma [19,20]. Some reports also revealed that PAK2 expression was closely associated with tumor malignancy and clinical outcome, which indicates that PAK2 may contribute to disease development and progression [20].…”

MiR-137: an important player in neural development and neoplastic transformation

“…94 Functional studies in several melanoma cell lines also revealed that miR-137 was able to inhibit melanoma cell invasion, migration, proliferation and induced apoptosis via downregulation of multiple target genes including transcription factor MITF and the oncogenes c-Met, YB1, EZH2 and PAK2, suggesting miR-137 involvement in several significant pathways in melanoma development and progression. 95, 96 Lower miR-137 expression contributed to poor survival in stage IV melanoma patients. 95 MiR-137 appears to also act as a tumor suppressor in colon cancer.…”

miR‐26a inhibits proliferation and promotes apoptosis in porcine immature Sertoli cells by targeting the PAK2 gene

“…The PAK2 gene belongs to the group I PAK family and is a part of the PAK serine/threonine kinase family, whose members were initially identified as binding partners for the Rho GTPases Cdc42 and Rac1. Previous studies reported that the PAK2 gene plays regulatory roles in various cellular processes, including proliferation (Deng et al, ; Siu et al, ; Zeng et al, ), apoptosis (Hao et al, ; Shao et al, ), migration (Deng et al, ; Gadepalli et al, ; Sato et al, ), survival (Zeng et al, ) and differentiation (Joseph et al, ; Zeng et al, ). In the present study, the PAK2 gene was determined to be a target gene of miR‐26a by luciferase reporter assay, and PAK2 mRNA and protein expression was found to be suppressed by miR‐26a in porcine Sertoli cells.…”