MicroRNA-18b inhibits the growth of malignant melanoma via inhibition of HIF-1α-mediated glycolysis

Abstract

Abstract. MicroRNAs (miRs) have been demonstrated to play critical roles in the development and progression of malignant melanoma (MM). However, the exact role and underlying mechanism of miR-18b in MM growth remains unclear. In the present study, real-time PCR data indicated that miR-18b was significantly downregulated in MM tissues compared to their matched adjacent non-tumor tissues. Low miR-18b expression was significantly associated with the tumor thickness and stage, although no significant association was observed between the miR-18b expression and the age, gender, or lymph node metastasis. Besides, miR-18b was also significantly downregulated in MM B16 and A375 cells compared to normal skin HACAT cells. Ectopic expression of miR-18b decreased the proliferation of A375 and B16 cells, while induced a remarkable cell cycle arrest at G1 stage. Besides, miR-18b overexpression also inhibited the glycolysis in A375 and B16 cells. HIF-1α, a key regulator in glycolysis, was then identified as a target gene of miR-18b, and its expression was negatively mediated by miR-18b in A375 and B16 cells. Overexpression of HIF-1α rescued the suppressive effect of miR-18b on MM cell proliferation and glycolysis. In vivo study further showed that overexpression of miR-18b inhibited the MM growth as well as the tumor-related death, accompanied with HIF-1α downregulation. Taken together, the present study suggests that miR-18b inhibits the growth of MM cells in vitro and in vivo through directly targeting HIF-1α.

MicroRNA‑18b acts as an oncogene in gastric cancer by directly targeting Kruppel‑like factor 6

“…miR-18b expression is dysregulated in several types of human cancer. miR-18b is downregulated in melanoma tissues and cell lines, and decreased levels are also significantly associated with tumor thickness and stage (15). Additionally, miR-18b has been reported to be upregulated in colorectal cancer.…”

“…Numerous studies have reported that miR-18b contributes to the malignant phenotype of cancers. Upregulation of miR-18b has been demonstrated to inhibit melanoma cell proliferation, migration, invasion, glycolysis and epithelial-to-mesenchymal transition in vitro, increase apoptosis in vitro and reduce tumor growth in vivo (15,28). miR-18b has been validated as an oncogene in colorectal cancer via participation in the regulation of cell cycle, proliferation and migration (16).…”

“…by directly targeting Kruppel-like factor 6 miRNAs in human cancers may provide promising therapeutic targets for antitumor therapy. The aberrant expression of miR-18b has been widely reported to occur in several types of human cancer (15)(16)(17). However, the expression pattern, biological role and specific functional mechanism of miR-18b in GC remains to be fully elucidated.…”

WITHDRAWN: Loss of miR-494 by exosomes promotes melanoma proliferation and metastasis

“…In recent years, accumulating evidence has revealed that miRNAs function as tumor suppressors or promoters. In our previous study, we confirmed that miR-33a, miR-199a, miR-18b, and miR-138 function as tumor suppressors by targeting oncogenes in melanoma Research Paper [9][10][11][12]. We interestingly found that miR-494 was abnormal low expression in melanoma cell than that in melanocytes via analyzing gene microarray results from Gene Expression Omnibus (GEO) datasets, suggesting miR-494 may play important role in melanoma progress.…”

Hypoxia-Inducible Factors and Cancer

“…They provided evidence of microRNA-18b binding to the HIF-1α 3′-UTR, while ectopic expression of this microRNA inhibited glycolysis and cell proliferation. [76, 77]. Hence HIF-1α coordinates multiple steps in glycolysis from glucose transport to lactate efflux allowing cancer cells satisfy their “addiction to glucose”.…”