MicroRNA-199a-5p inhibits tumor proliferation in melanoma by mediating HIF-1α

Abstract

The expression of hypoxia-inducible factor 1α (HIF-1α) is often abundant in human cancer and it is associated with poor prognosis. The present study aimed to investigate its regulation by microRNA (miRNA). The expression of miRNA-199a-5p (miR-199a-5p) in melanoma was detected by quantitative polymerase chain reaction on samples from 25 melanoma patients. The target of miR-199a-5p was predicted and demonstrated by a dual‑luciferase reporter system. The effects of miR-199a-5p on melanoma cells were assayed in B16 and HME1 melanoma cell lines. Furthermore, the potential of miR‑199a‑5p as a therapeutic target was illustrated in xenograft nude mice models. Low expression of miR‑199a‑5p in tumor melanoma tissue samples from patients was associated with high histological grade and advanced tumor stage. The 3'-untranslated region of HIF‑1α was identified as a target of miR‑199a‑5p by Targetscan software. The dual-luciferase reporter assay demonstrated that miR‑199a‑5p transfection of mimics decreased the luciferase activity significantly (P<0.05). In the B16 and HME1 cell lines, overexpression of miR‑199a‑5p suppressed cell proliferation and arrested the cell cycle in the G1 phase. In vivo overexpression of miR‑199a‑5p significantly suppressed xenograft growth and downregulated the expression of HIF‑1α (P<0.05). The results from the present study suggest that miR‑199a‑5p suppressed melanoma proliferation via HIF‑1α, suggesting it may be a potential therapeutic target for melanoma treatment.

Exposure of Endothelium to Biomimetic Flow Waveforms Yields Identification of miR-199a-5p as a Potent Regulator of Arteriogenesis

“…To date, miR-199a has been mostly studied for its roles in cardiac hypertrophy,46, 47 smooth muscle proliferation, 48 angiogenesis,49, 50, 51, 52, 53, 54 and as a tumor suppressor in a variety of cancers 29, 50, 52, 55, 56, 57, 58, 59. However, miR-199a also regulates several genes important for arteriogenesis via direct seed sequence binding to target mRNAs.…”

MicroRNA-320 regulates autophagy in retinoblastoma by targeting hypoxia inducible factor-1α

“…The results suggested an association between miR-320 and HIF-1α in adjusting RB progression. Increasing evidence has shown that miRNA interfere with the metastasis and invasion of various types of cancer via the regulation of HIF-1α (21)(22)(23)(24). In this study, a luciferase reporter assay was employed to investigate the effect of miR-320 on HIF-1α.…”

MiR‐199a‐5p suppresses tumorigenesis by targeting clathrin heavy chain in hepatocellular carcinoma

“…It is well known that miRNAs function via regulating their target protein by binding to the 3’ untranslated regions (UTRs) of target messenger RNAs (mRNAs), resulting in mRNA degradation or the blockade of mRNA translation . Previously, miR‐199a‐5p was reported to functions as a tumor suppressor by targeting connective tissue growth factor (CTGF), integrin β1, hypoxia‐inducible factor 1 alpha (HIF‐1α), E‐cadherin, hexokinase 2, frizzled class receptor 6 (FZD6), E2F transcription factor 3 (E2F3), Wnt family member 2 (WNT2) and cyclin‐dependent kinase inhibitor 1C (P57, CDKN1C) …”

“…In present study, we showed that miR-199a-5p, frequently down- 19,20 Previously, miR-199a-5p was reported to functions as a tumor suppressor by targeting connective tissue growth factor (CTGF), integrin β1, hypoxia-inducible factor 1 alpha (HIF-1α), E-cadherin, hexokinase 2, frizzled class receptor 6 (FZD6), E2F transcription factor 3 (E2F3), Wnt family member 2 (WNT2) and cyclin-dependent kinase inhibitor 1C (P57, CDKN1C). [21][22][23][24][25][26][27][28][29] Clathrin is considered the prototype vesicle coat protein whose self-assembly mediates sorting of membrane cargo and recruitment of lipid modifiers. 30 In the past decades, most of studies were focused on clathrin mediated endocytosis.…”