MicroRNA-486-3p promotes the proliferation and metastasis of cutaneous squamous cell carcinoma by suppressing flotillin-2
MicroRNA-486-3p promotes the proliferation and metastasis of cutaneous squamous cell carcinoma by suppressing flotillin-2
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DOI：
10.1016/j.jdermsci.2021.11.005
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发表时间：
2022-01-25
影响因子：
4.6
通讯作者：
Zhen, Peilin
中科院分区：
文献类型：
--
作者：
Li, Xiangzhi;Yuan, Yawen;Zhen, Peilin
背景资料：miR-486- 3 p的异常调控与多种肿瘤的生长和发展有关，但miR-486- 3 p在皮肤鳞状细胞癌（cSCC）中的特异性功能尚未得到证实。目的：本研究旨在验证miR-486- 3 p在cSCC中的潜在分子机制以及miR-486- 3 p作为未来治疗新靶点的潜力。研究方法：采用荧光原位杂交（FISH）和定量逆转录PCR（qRTPCR）方法检测miR 486 - 3 p和FLOT 2在人cSCC和正常皮肤组织中的表达水平。与BALB/C裸鼠肿瘤模型一样，利用HSC-1、HSC-5和A431三种cSCC细胞系来证明miR-486- 3 p和FLOT 2在肿瘤发生中的潜在功能。结果：miR-486- 3 p在cSCC组织和细胞系中均呈高表达。上调miR-486- 3 p可增强cSCC细胞系的增殖和迁移能力，并促进体内致瘤性。进一步证实FLOT 2是miR-486- 3 p的直接靶基因。与miR-486- 3 p的表达水平相反，FLOT 2在cSCC患者标本和细胞系中低表达。FLOT 2的敲低促进了cSCC的肿瘤发生;而FLOT 2逆转了miR-486- 3 p的肿瘤促进作用。结论：miR-486- 3 p作为癌基因通过抑制FLOT 2在cSCC中发挥作用。这一发现将开发新的cSCC治疗靶点。(c)2021日本皮肤病研究学会。Elsevier B. V.出版，保留所有权利。
Background: Dysregulation of miR-486-3p was related to the growth and development of a variety of cancers, but the specific function of miR-486-3p in cutaneous squamous cell carcinoma (cSCC) is not to be confirmed yet. Objective: Our present study aimed to validate the potential molecular mechanisms of miR-486-3p in cSCC and the potential of miR-486-3p as a novel target for future treatment. Methods: Human cSCC samples and normal skin tissues were applied to determine the expression level of miR486-3p and FLOT2 by fluorescence in situ hybridization (FISH) and quantitative reverse transcription PCR (qRTPCR), respectively. As well as BALB/C nude mouse tumor model, three cSCC cells lines including HSC-1, HSC-5 and A431 were utilized to demonstrate the potential function of miR-486-3p and FLOT2 in tumorigenesis. Results: Our experimental results showed that miR-486-3p was highly expressed both in tumor samples and cell lines of cSCC. Upregulation of miR-486-3p enhanced the proliferation and migration ability of cSCC cell lines and promoted tumorigenicity in vivo. Furthermore, we confirmed that FLOT2 was a direct targeted gene of miR-486-3p. In contrary to the expression level of miR-486-3p, FLOT2 was low expressed in cSCC patient specimens and cell lines. Knockdown of FLOT2 promoted tumorigenesis of cSCC; whereas FLOT2 reversed the tumor-promoting effect of miR-486-3p. Conclusion: Our data exhibited that miR-486-3p exerted its effects on carcinogenesis as an oncogene in cSCC via suppression of FLOT2. This discovery will develop new therapeutic targets of cSCC. (c) 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.