miR-381-3p通过靶向同源盒A9减弱人间变性甲状腺癌的阿霉素耐药性

IF 1.8 4区 医学 Q3 PATHOLOGY International Journal of Experimental Pathology Pub Date : 2021-10-31 DOI:10.1111/iep.12401
Yan Zhang, Ke Li, Weili Wang, Jingjing Han
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引用次数: 3

摘要

microRNA (miR)的异常表达经常被报道与癌症相关的耐药有关。在这里,我们计划研究miR-381-3p是否有助于间变性甲状腺癌(ATC)中阿霉素(DOX)的耐药。制备抗dox的ATC组织和细胞系,检测miR-381-3p和同源盒A9 (HOXA9)的表达。体外实验采用CCK8、transwell和TUNEL检测细胞增殖、迁移侵袭和凋亡情况。与良性甲状腺组织相比,HOXA9在ATC组织中表达强烈。与亲本ATC细胞系相比,HOXA9蛋白在抗dox的SW1736和CAL62细胞中的表达显著上调。HOXA9的敲低导致dox耐药SW1736和CAL62细胞的生长抑制和凋亡。我们的研究结果还表明,在dox抗性ATC组织和细胞系中,miR-381-3p表达水平显著降低。miR-381-3p可能作为肿瘤抑制因子,通过抑制HOXA9蛋白表达,抑制dox耐药SW1736和CAL62细胞的增殖、迁移和侵袭,诱导细胞凋亡。我们的研究结果提出了一种新的信号轴miR-381-3p/HOXA9,它介导ATC中的DOX抗性。miR-381-3p和HOXA9可能是预防ATC进展和耐药的有希望的分子靶点。
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miR-381-3p attenuates doxorubicin resistance in human anaplastic thyroid carcinoma via targeting homeobox A9

Abnormal microRNA (miR) expression has frequently been reported to be implicated in cancer-related drug resistance. Herein, we planned to investigate whether miR-381-3p contributes to doxorubicin (DOX) resistance in anaplastic thyroid carcinoma (ATC). DOX-resistant ATC tissues and cell lines were prepared to detect miR-381-3p and homeobox A9 (HOXA9) expression. CCK8, transwell and TUNEL assays were performed to evaluate cell proliferation, migration and invasion, and apoptosis in in vitro experiments. HOXA9 expression is intensively expressed in ATC tissues compared with benign thyroid tissues. Compared with parental ATC cell lines, HOXA9 protein expression is significantly up-regulated in DOX-resistant SW1736 and CAL62 cells. The knockdown of HOXA9 leads to growth inhibition and apoptosis of DOX-resistant SW1736 and CAL62 cells. Our results also indicate a significant decrease in miR-381-3p expression levels in DOX-resistant ATC tissues and cell lines. miR-381-3p may function as a tumour suppressor to impede proliferation, migration and invasion and induce apoptosis of DOX-resistant SW1736 and CAL62 cells by inhibiting HOXA9 protein expression. Our results present a novel signalling axis miR-381-3p/HOXA9 that mediates DOX resistance in ATC. miR-381-3p and HOXA9 may be promising molecular targets for preventing ATC progression and drug resistance.

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来源期刊
CiteScore
4.50
自引率
3.30%
发文量
35
审稿时长
>12 weeks
期刊介绍: Experimental Pathology encompasses the use of multidisciplinary scientific techniques to investigate the pathogenesis and progression of pathologic processes. The International Journal of Experimental Pathology - IJEP - publishes papers which afford new and imaginative insights into the basic mechanisms underlying human disease, including in vitro work, animal models, and clinical research. Aiming to report on work that addresses the common theme of mechanism at a cellular and molecular level, IJEP publishes both original experimental investigations and review articles. Recent themes for review series have covered topics as diverse as "Viruses and Cancer", "Granulomatous Diseases", "Stem cells" and "Cardiovascular Pathology".
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