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长链非编码RNA LINC00665通过调控miR-224-5p/VMA21轴促进黑色素瘤细胞的生长和迁移。

Long non-coding RNA LINC00665 promotes melanoma cell growth and migration via regulating the miR-224-5p/VMA21 axis.

作者信息

Wang Xiaonan, Wang Yanbing, Lin Feifei, Xu Meng, Zhao Xin

机构信息

Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, China.

出版信息

Exp Dermatol. 2022 Jan;31(1):64-73. doi: 10.1111/exd.14246. Epub 2020 Dec 12.

DOI:10.1111/exd.14246
PMID:33247967
Abstract

Melanoma is an aggressive malignant skin tumor endangering the health of patients. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been increasingly reported to be implicated in the carcinogenesis of melanoma. Long intergenic non-coding RNA 00665 (LINC00665) has been found to exert important regulatory roles in some cancers, yet its function in melanoma remains to be investigated. QRT-PCR analysis was conducted to evaluate the relative expression of RNAs. Functional experiments in vitro including colony formation, EdU, wound-healing and transwell assays, as well as in vivo xenograft assays, were utilized to study the role of LINC00665 in melanoma. Mechanical experiments were implemented to probe into the molecular linkage of LINC00665, miR-224-5p and VMA21. LINC00665 was abnormally highly expressed in melanoma cells. Silencing LINC00665 could inhibit the proliferation and migration of melanoma cells. LINC00665 sponged miR-224-5p to upregulate VMA21. VMA21 knockdown exerted similarly interfering effects on above biological processes in melanoma cells. However, VMA21 overexpression abolished the in vitro and in vivo outcomes of LINC00665 silencing. LINC00665 promotes proliferative and migrating abilities of melanoma cells via targeting miR-224-5p/VMA21 axis.

摘要

黑色素瘤是一种侵袭性恶性皮肤肿瘤,危及患者健康。越来越多的研究报道长链非编码RNA(lncRNAs)和微小RNA(miRNAs)与黑色素瘤的致癌作用有关。长链基因间非编码RNA 00665(LINC00665)已被发现在某些癌症中发挥重要的调控作用,但其在黑色素瘤中的功能仍有待研究。进行QRT-PCR分析以评估RNA的相对表达。利用包括集落形成、EdU、伤口愈合和Transwell实验在内的体外功能实验以及体内异种移植实验,研究LINC00665在黑色素瘤中的作用。进行机制实验以探究LINC00665、miR-224-5p和VMA21之间的分子联系。LINC00665在黑色素瘤细胞中异常高表达。沉默LINC00665可抑制黑色素瘤细胞的增殖和迁移。LINC00665通过吸附miR-224-5p上调VMA21。敲低VMA21对黑色素瘤细胞的上述生物学过程产生类似的干扰作用。然而,VMA21过表达消除了LINC00665沉默的体外和体内实验结果。LINC00665通过靶向miR-224-5p/VMA21轴促进黑色素瘤细胞的增殖和迁移能力。

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