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miR-326 通过靶向 MAPK1 和 ERBB4 抑制甲状腺乳头状癌的进展。

miR-326 inhibits the progression of papillary thyroid carcinoma by targeting MAPK1 and ERBB4.

机构信息

Department of Endocrinology, Shenzhen Longhua District Central Hospital, Shenzhen, China.

出版信息

Neoplasma. 2020 May;67(3):604-613. doi: 10.4149/neo_2020_190731N696. Epub 2020 Apr 7.

Abstract

Papillary thyroid carcinoma (PTC) is the prevalent histotype of thyroid cancer, with increasing incidence worldwide. MicroRNAs (miRNAs) could play an important role in the development and progression of human cancers. Interestingly, miR-326 was validated as one of the downregulated miRNAs in PTC. Therefore, it is necessary to research the function of miR-326 involved in the progression of PTC. In the current study, we detected the downregulation of miR-326 in PTC tissues and cell lines. The miR-326 overexpression or knockdown was conducted in TPC-1 or HTh83 PTC cells. miR-326 mimics decreased the proliferation, clone formation ability and caused G1-phase accumulation. In addition, the reduction of migration and invasion abilities was induced by miR-326 mimics. Western blot analysis showed that the cells with miR-326 mimics exhibited the inhibition of vimentin and N-cadherin, as well as enhancement of E-cadherin. Importantly, miR-326 could directly target mitogen activated protein kinase 1 (MAPK1) and epidermal growth factor receptor 4 (ERBB4). MAPK1 or ERBB4 overexpression rescued the effects of miR-326 on proliferation, migration, and invasion in PTC cells. Notably, miR-326 reduced tumorigenesis in vivo, including the decrease of tumor volume and weight, suppression of Ki-67, N-cadherin, MAPK1 and ERBB4. In all, these results might provide a new therapeutic target for the diagnosis of PTC.

摘要

甲状腺乳头状癌(PTC)是甲状腺癌中最常见的组织学类型,其发病率在全球范围内呈上升趋势。微小 RNA(miRNA)可能在人类癌症的发生和发展中发挥重要作用。有趣的是,miR-326 被证实是 PTC 下调的 miRNA 之一。因此,研究 miR-326 在 PTC 进展中所涉及的功能是必要的。在本研究中,我们检测到 PTC 组织和细胞系中 miR-326 的下调。在 TPC-1 或 HTh83 PTC 细胞中进行 miR-326 的过表达或敲低。miR-326 模拟物降低了增殖、克隆形成能力,并导致 G1 期积累。此外,miR-326 模拟物诱导迁移和侵袭能力降低。Western blot 分析表明,miR-326 模拟物的细胞表现出波形蛋白和 N-钙粘蛋白的抑制,以及 E-钙粘蛋白的增强。重要的是,miR-326 可以直接靶向丝裂原活化蛋白激酶 1(MAPK1)和表皮生长因子受体 4(ERBB4)。MAPK1 或 ERBB4 的过表达挽救了 miR-326 对 PTC 细胞增殖、迁移和侵袭的影响。值得注意的是,miR-326 减少了体内肿瘤发生,包括肿瘤体积和重量的减少、Ki-67、N-钙粘蛋白、MAPK1 和 ERBB4 的抑制。总之,这些结果可能为 PTC 的诊断提供新的治疗靶点。

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