PMID- 34117611 OWN - NLM STAT- MEDLINE DCOM- 20211227 LR - 20211227 IS - 1749-0774 (Electronic) IS - 0914-7470 (Linking) VI - 34 IP - 5 DP - 2021 Sep TI - Suppressive role of microRNA-130b-3p in ferroptosis in melanoma cells correlates with DKK1 inhibition and Nrf2-HO-1 pathway activation. PG - 1532-1544 LID - 10.1007/s13577-021-00557-5 [doi] AB - Cell death pathways related to ferroptosis are implicated in the progression of melanoma. Emerging data reporting the upregulation of microRNA (miR)-130b-3p in melanoma indicate the potential implication of miR-130b-3p in this malignancy. Herein, we aimed to identify whether and how miR-130b-3p regulated ferroptosis in melanoma cells. Melanoma cells (A375, G-361) were treated with erastin or RSL3 to mimic ferroptosis in vitro. Viability, lipid peroxidation level and ferrous ion content in melanoma cells were then assessed in response to manipulation of miR-130b-3p expression. Luciferase assay was conducted to determine the binding of miR-130b-3p to Dickkopf1 (DKK1). Western blot assay was conducted to determine the expression of molecules related to nuclear factor-erythroid 2 p45-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. The results indicated that miR-130b-3p exerted an inhibitory role in erastin or RSL3-induced ferroptosis, evidenced by reductions in lipid peroxidation and ferrous ion content. By suppressing the expression of target gene DKK1, miR-130b-3p activated the Nrf2/HO-1 pathway, whereby repressing ferroptosis. miR-130b-3p blocked the antitumor activity of erastin. Further, in vitro findings were reproduced in an in vivo murine model. Together, these data suggest the potential of miR-130b-3p to inhibit ferroptosis in melanoma cells and the mechanism was related to DKK1-mediated Nrf2/HO-1 pathway. CI - (c) 2021. Japan Human Cell Society. FAU - Liao, Yangying AU - Liao Y AD - Department of Dermatology, Hunan Provincial People's HospitalThe First Affiliated Hospital of Hunan Normal University)Hunan Province, No. 61, Jiefang West Road, Changsha, 410005, People's Republic of China. FAU - Jia, Xiaomin AU - Jia X AD - Department of Pathology, Lhasa People's Hospital of Tibet Autonomous Region, Lhasa, 850000, People's Republic of China. FAU - Ren, Yi AU - Ren Y AD - Beijing Jishuitan Hospital, Beijing, 100035, People's Republic of China. FAU - Deji, Zhuoga AU - Deji Z AD - Department of Pathology, Lhasa People's Hospital of Tibet Autonomous Region, Lhasa, 850000, People's Republic of China. FAU - Gesang, Yuzhen AU - Gesang Y AD - Department of Pathology, Lhasa People's Hospital of Tibet Autonomous Region, Lhasa, 850000, People's Republic of China. FAU - Ning, Ning AU - Ning N AD - Medical Department, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, People's Republic of China. FAU - Feng, Hao AU - Feng H AD - Department of Dermatology, Hunan Provincial People's HospitalThe First Affiliated Hospital of Hunan Normal University)Hunan Province, No. 61, Jiefang West Road, Changsha, 410005, People's Republic of China. doctorfenghao@hunnu.edu.cn. FAU - Yu, Hong AU - Yu H AD - Department of Pathology, The Third People's Hospital of Shenzhen, Shenzhen, 518100, People's Republic of China. FAU - Wei, An AU - Wei A AD - Department of Ultrasound, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), No. 61, Jiefang West Road, Changsha, 410005, Hunan Province, People's Republic of China. linshiwei06@163.com. LA - eng GR - 20C1125/Hunan Provincial Education Department Project/ GR - BSJJ202008/Doctor's Fund Project of Hunan Provincial People's Hospital/ GR - No kq2014202/Changsha Municipal Science and Technology Bureau Natural Science Foundation Project/ PT - Journal Article DEP - 20210611 PL - Japan TA - Hum Cell JT - Human cell JID - 8912329 RN - 0 (DKK1 protein, human) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (MicroRNAs) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NFE2L2 protein, human) RN - EC 1.14.14.18 (HMOX1 protein, human) RN - EC 1.14.14.18 (Heme Oxygenase-1) SB - IM MH - Cell Line, Tumor MH - Ferroptosis/*genetics MH - Heme Oxygenase-1/*genetics/*metabolism MH - Humans MH - Intercellular Signaling Peptides and Proteins/*genetics/*metabolism MH - Melanoma/*genetics/*pathology MH - MicroRNAs/*genetics/*physiology MH - NF-E2-Related Factor 2/*genetics/*metabolism MH - Signal Transduction/*genetics/physiology OTO - NOTNLM OT - DKK1 OT - Ferroptosis OT - Iron accumulation OT - Lipid peroxidation OT - Melanoma OT - Nrf2/HO-1 pathway OT - microRNA-130b EDAT- 2021/06/13 06:00 MHDA- 2021/12/28 06:00 CRDT- 2021/06/12 06:19 PHST- 2021/02/01 00:00 [received] PHST- 2021/05/24 00:00 [accepted] PHST- 2021/06/13 06:00 [pubmed] PHST- 2021/12/28 06:00 [medline] PHST- 2021/06/12 06:19 [entrez] AID - 10.1007/s13577-021-00557-5 [pii] AID - 10.1007/s13577-021-00557-5 [doi] PST - ppublish SO - Hum Cell. 2021 Sep;34(5):1532-1544. doi: 10.1007/s13577-021-00557-5. Epub 2021 Jun 11.