HEG1-responsive microRNA-23b regulates cell proliferation in malignant mesothelioma cells
HEG1-responsive microRNA-23b regulates cell proliferation in malignant mesothelioma cells
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DOI：
10.1016/j.bbrc.2020.03.172
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发表时间：
2020-06-11
影响因子：
3.1
通讯作者：
Ohbayashi, Chiho
中科院分区：
文献类型：
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作者：
Fujii, Tomomi;Itami, Hiroe;Ohbayashi, Chiho
恶性间皮瘤（malignant mesothelioma，MM）是一种致死性肿瘤，缺乏特异性诊断标志物和/或致病分子靶向药物是其病理诊断和靶向治疗的主要问题。由于MM中未知的存活、死亡和细胞毒性信号，MM的分子靶点尚未阐明。HEG同源物1（HEG 1）是含有表皮生长因子样结构域的粘蛋白样膜蛋白，并且其通过异常信号传导（包括细胞粘附期间的信号传导）以及通过保护免受肿瘤细胞侵袭而在癌症中起重要作用。HEG 1表达支持MM细胞的生存和增殖。在这项研究中，使用MM细胞系（H226，MESO 4，H2052）进行了HEG 1和microRNA的功能分析。MTS测定显示，在用microRNA-23 b（miR-23 b）抑制剂和/或HEG 1 siRNA瞬时转染后，细胞增殖显著降低。膜联蛋白V测定揭示了在抑制miR-23 b和/或HEG 1后诱导细胞凋亡。Western blotting显示，自噬相关蛋白LC 3-II在miR-23 b和/或HEG 1抑制后被诱导。这些结果表明，miR-23 b通过逃避MM细胞中由凋亡和自噬诱导的细胞毒性而有助于HEG 1依赖性细胞增殖。因此，HEG 1依赖/介导的miR-23 b信号传导可能是MM诊断和治疗的潜在靶点。(C)2020爱思唯尔公司All rights reserved.
Malignant mesothelioma (MM) is a fatal tumor, and the absence of a specific diagnostic marker and/or a pathogenic molecule-targeting drug is a major issue for its pathological diagnosis and for targeting therapy. The molecular target of MM has not been elucidated because of unknown survival, death, and cytotoxic signals in MM. HEG homolog 1 (HEG1) is a mucin-like membrane protein that contains epidermal growth factor-like domains, and it plays an important role in cancers through aberrant signaling, including that during cell adhesion, as well as through protection from invasion of tumor cells. HEG1 expression supports the survival and proliferation of MM cells. In this study, functional analysis of HEG1 and microRNAs using MM cell lines (H226, MESO4, H2052) was performed. The MTS assay revealed that cell proliferation was significantly reduced upon transient transfection with microRNA-23b (miR-23b) inhibitor and/or HEG1 siRNA. The Annexin V assay revealed that apoptosis was induced upon suppression of miR-23b and/or HEG1. Western blotting showed that the autophagy-related protein LC3-II was induced upon suppression of miR-23b and/or HEG1. These results revealed that miR-23b contributes to HEG1-dependent cell proliferation through evasion of cytotoxicity induced by apoptosis and auto-phagy in MM cells. HEG1-dependent/mediated miR-23b signaling may therefore be a potential target for MM diagnosis and therapy. (C) 2020 Elsevier Inc. All rights reserved.