Identification of extracellular vesicles-transported miRNAs in Erlotinib-resistant head and neck squamous cell carcinoma
Identification of extracellular vesicles-transported miRNAs in Erlotinib-resistant head and neck squamous cell carcinoma
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厄洛替尼耐药头颈鳞状细胞癌中细胞外囊泡转运 miRNA 的鉴定
DOI：
10.1007/s12079-020-00546-7
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发表时间：
2020-03
影响因子：
4.1
通讯作者：
Song Xiaomeng
中科院分区：
文献类型：
--
作者：
Zheng Yang;Song An;Zhou Yan;Zhong Yi;Zhang Wei;Wang Chundi;Ding Xu;Du Yifei;Zhang Wei;Li Gang;Wu Heming;Wu Yunong;Song Xiaomeng
厄洛替尼是一种表皮生长因子受体（EGFR）途径的口服酪氨酸激酶抑制剂。虽然我们之前的研究已经证明了厄洛替尼在头颈部鳞状细胞癌（HNSCC）中的疗效，但迄今为止，它也显示出不良的临床反应率和令人失望的HNSCC临床试验结果。在这项研究中，我们发现在厄洛替尼耐药的HNSCC细胞中细胞增殖和侵袭能力升高。本研究探讨了细胞外囊泡（EVs）中miRNA在化疗耐药形成过程中的作用。在来自耐药细胞的EV中上调的miRNA中，miR-7704、miR-21- 5 p和miR-3960在转染后显示出最多的促肿瘤发生改变。相反，let-7i-5 p、miR-619- 5 p和miR-30 e-3 p表现出肿瘤抑制作用。通过qRT-PCR和Western blot分析，我们发现波形蛋白在调节厄洛替尼耐药性中起关键作用。此外，免疫系统在GO和KEGG分析中突出显示。转染miR-7704、miR-21- 5 p显著提高CTLA-4和LAG 3 mRNA水平。同时，miR-3960可增加HNSCC细胞中TIM 3的相对mRNA表达。let-7i-5 p、miR-619- 5 p和miR-30 e-3 p的转染降低了这些检查点因子。总之，本研究描述了EV传播的miRNA在厄洛替尼耐药中的作用。靶向失调的免疫系统可能是克服HNSCC细胞中厄洛替尼耐药性的有效方法。
Erlotinib is an oral tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) pathway. Although our previous study has proved the efficacy of Erlotinib in head and neck squamous cell carcinoma (HNSCC), it has also demonstrated poor clinical response rates and disappointing results in clinical trials for HNSCC to date. In this study, we discovered elevated cell proliferation and invasion ability in erlotinib-resistant HNSCC cells. The contributions of miRNAs within extracellular vesicles (EVs) during the formation of chemoresistance were investigated in this study. Among up-regulated miRNAs in EVs derived from resistant cells, miR-7704, miR-21-5p and miR-3960 showed the most pro-tumorigenic alterations after transfection. Conversely, let-7i-5p, miR-619-5p and miR-30e-3p demonstrated tumor suppressive effects. By performing qRT-PCR and Western blot analysis, we found Vimentin played a pivotal role in modulating erlotinib resistance. Additionally, immune system was highlighted in the GO and KEGG analyses. Transfection of miR-7704, miR-21-5p significantly elevated CTLA-4 and LAG3 mRNA levels. Meanwhile, miR-3960 increased the relative mRNA expression of TIM3 in HNSCC cells. Transfection of let-7i-5p, miR-619-5p and miR-30e-3p decreased these checkpoint factors. To conclude, the present study described the roles of EVs-transmitted miRNAs on erlotinib resistance. Targeting the disregulated immune system could be the effective method to overcome erlotinib-resistance in HNSCC cells.
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影响因子：
64.5
作者：
Boelens MC;Wu TJ;Nabet BY;Xu B;Qiu Y;Yoon T;Azzam DJ;Twyman-Saint Victor C;Wiemann BZ;Ishwaran H;Ter Brugge PJ;Jonkers J;Slingerland J;Minn AJ
通讯作者：
Minn AJ
DOI：
10.1002/hed.24313
发表时间：
2016-04
期刊：
Head & neck
影响因子：
--
作者：
Yao M;Woods C;Lavertu P;Fu P;Gibson M;Rezaee R;Zender C;Wasman J;Sharma N;Machtay M;Savvides P
通讯作者：
Savvides P
DOI：
10.1007/978-3-030-24517-7_3
发表时间：
2019
期刊：
Tissue Engineering in Oral and Maxillofacial Surgery
影响因子：
--
作者：
Bettina Mannerström;S. Kaur;Riitta Seppänen-Kaijansinkko
通讯作者：
Bettina Mannerström;S. Kaur;Riitta Seppänen-Kaijansinkko
影响因子：
9
作者：
通讯作者：
--
影响因子：
7.2
作者：
Noman, Muhammad Zaeem;Janji, Bassam;Chouaib, Salem
通讯作者：
Chouaib, Salem