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微小RNA-650通过靶向生长抑制家族成员4促进黑色素瘤转移。

MicroRNA-650 promotes melanoma metastasis via targeting inhibitor of growth family member 4.

作者信息

Chen Chen, Liu Jing, Ma Yanli, Wang Yu, Cai Limin

机构信息

Department of Dermatology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150001, China.

出版信息

Heliyon. 2024 Aug 13;10(16):e36199. doi: 10.1016/j.heliyon.2024.e36199. eCollection 2024 Aug 30.

Abstract

OBJECTIVE

This study aimed to evaluate the effects of microRNA-650 (miR-650) on melanoma metastasis and reveal the regulatory relationship between miR-650 and the inhibitor of growth family member 4 (ING4).

METHODS

miR-650 expression was determined in human melanoma WM115 and A-375 cells. WM115 cells were transfected with miR-650 mimic or mimic control. The invasion and migration abilities of transfected WM115 cells were analyzed using Transwell and wound healing assays, respectively. Then, miR-650-overexpression lentivirus vector was constructed and transfected into WM115 cells. After injection into the mice, the number of micro-metastatic foci in the lung tissues was counted. A regulatory relationship between miR-650 and ING4 was identified in WM115 and A-375 cells.

RESULTS

The miR-650 expression was upregulated in WM115 and A-375 cells. WM115 cells transfected with the miR-650 mimic exhibited higher invasive and migratory abilities than mock cells or cells transfected with negative control (NC). The number of micro-metastatic foci was significantly higher in mice injected with Lenti-miR-650 than that in those injected with mock or NC controls. Transfection with miR-650 mimic observably inhibited the expression of ING4 in WM115 and A-375 cells, whereas transfection with miR-650 inhibitor had the opposite effect. Dual-luciferase reporter gene assay showed that the miR-650 mimic inhibited the luciferase activity of ING4.

CONCLUSION

miR-650 promotes melanoma metastasis by downregulating ING4 expression.

摘要

目的

本研究旨在评估微小RNA - 650(miR - 650)对黑色素瘤转移的影响,并揭示miR - 650与生长抑制家族成员4(ING4)之间的调控关系。

方法

测定人黑色素瘤WM115和A - 375细胞中miR - 650的表达。用miR - 650模拟物或模拟对照转染WM115细胞。分别采用Transwell和伤口愈合试验分析转染后WM115细胞的侵袭和迁移能力。然后,构建miR - 650过表达慢病毒载体并转染至WM115细胞。注射到小鼠体内后,计数肺组织中的微转移灶数量。在WM115和A - 375细胞中鉴定miR - 650与ING4之间的调控关系。

结果

WM115和A - 375细胞中miR - 650表达上调。用miR - 650模拟物转染的WM115细胞比未处理细胞或用阴性对照(NC)转染的细胞表现出更高的侵袭和迁移能力。注射Lenti - miR - 650的小鼠肺组织中的微转移灶数量明显高于注射未处理或NC对照的小鼠。用miR - 650模拟物转染可显著抑制WM115和A - 375细胞中ING4的表达,而用miR - 650抑制剂转染则产生相反的效果。双荧光素酶报告基因检测表明,miR - 650模拟物抑制了ING4的荧光素酶活性。

结论

miR - 650通过下调ING4表达促进黑色素瘤转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a650/11382039/7aa24783c16e/gr1.jpg

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