Downregulation of ARMC8 promotes tumorigenesis through activating Wnt/β-catenin pathway and EMT in cutaneous squamous cell carcinomas
Downregulation of ARMC8 promotes tumorigenesis through activating Wnt/β-catenin pathway and EMT in cutaneous squamous cell carcinomas
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DOI：
10.1016/j.jdermsci.2021.05.002
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发表时间：
2021-06-19
影响因子：
4.6
通讯作者：
Zhou, Meijuan
中科院分区：
文献类型：
--
作者：
Li, Xiangzhi;Zhang, Chen;Zhou, Meijuan
背景：犰狳重复序列8（ARMC8）的异常表达在多种癌症的肿瘤生长和转移中发挥着至关重要的作用。 ARMC8在皮肤鳞状细胞癌（cSCC）中的具体作用尚未阐明。目的：本研究旨在探讨ARMC8和上皮间质转化（EMT）在cSCC发展中的分子机制，为未来的治疗提供转化思路。方法：采用cSCC肿瘤标本，通过免疫组化法检测ARMC8。利用包括 HSC-1、HSC-5 和 A431 在内的三种 cSCC 细胞系以及 BALB/C 小鼠肿瘤模型来研究肿瘤发生的潜在机制。结果：我们的数据确定 ARMC8 是 miR-664 的直接下游靶标。我们发现 ARMC8 在 cSCC 患者标本和 cSCC 细胞系中表达显着低。 ARMC8 的敲低可促进致瘤行为，例如体外细胞增殖、迁移和侵袭能力增加，以及异种移植小鼠模型中的致瘤性增强。而 ARMC8 过表达会抑制 cSCC 中的肿瘤发生。总之，它揭示了ARMC8通过抑制cSCC中的Wnt/β-catenin通路和上皮-间质转化而发挥肿瘤抑制因子的作用。结论：我们的数据证实ARMC8的异常表达在cSCC的癌变过程中起着至关重要的作用。 ARMC8 的过度表达将促进 cSCC 治疗干预措施的未来发展。 (C) 2021 年日本皮肤病研究学会。由 Elsevier B.V. 出版。保留所有权利。
Background: Aberrant expression of Armadillo repeat containing 8 (ARMC8) plays crucial roles in tumor growth and metastasis of various cancers. The specific role of ARMC8 in cutaneous squamous cell carcinoma (cSCC) is yet to be elucidated.Objective: The present study aimed to investigate the molecular mechanisms of ARMC8 and epithelial-mesenchymal transition (EMT) in cSCC development and provide translational insights for future therapeutics.Methods: cSCC tumor specimens were used to determine the ARMC8 by immunohistochemistry. Three cSCC cell lines including HSC-1, HSC-5 and A431 as well as BALB/C mouse tumor model was utilized to study the potential mechanisms in tumorigenesis.Results: Our data identified ARMC8 as a direct downstream target of miR-664. We found that ARMC8 was remarkably low expression in cSCC patient specimens and cSCC cell lines. Knockdown of ARMC8 promotes tumorigenic behaviors such as increased cell proliferation, migration and invasion capacities in vitro and enhanced tumorigenicity in xenograft mouse model. Whereas ARMC8 over-expression inhibits tumorigenesis in cSCC. Together, it revealed ARMC8 functions as a tumor suppressor via restraining Wnt/beta-catenin pathway and epithelial-mesenchymal transition in cSCC.Conclusion: Our data verifies that aberrant expression of ARMC8 plays a vital role in carcinogenesis of cSCC. And overexpression of ARMC8 will facilitate future development of cSCC therapeutic interventions. (C) 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.