MicroRNA-21 induces cisplatin resistance in head and neck squamous cell carcinoma.
MicroRNA-21 induces cisplatin resistance in head and neck squamous cell carcinoma.
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DOI：
10.1371/journal.pone.0267017
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Ji, Yongsheng
中科院分区：
文献类型：
--
作者：
Sheng, Shuyan;Su, Wenzhuo;Mao, Deshen;Li, Conghan;Hu, Xinyang;Deng, Wanyu;Yao, Yong;Ji, Yongsheng
药物抗性，无论是内在的还是获得性的，都可能损害治疗效果并导致细胞运动性增加和死亡。MicroRNA-21（miR-21）是一种原癌基因，可促进癌细胞耐药性的发展或维持。恢复药物敏感性可以改善治疗策略，这种可能性需要功能评估和机制探索。对于miR-21检测，获得来自30名头颈部鳞状细胞癌（HNSCC）患者和8个头颈部癌（HNC）细胞系的匹配组织样品。采用逆转录-PCR检测蛋白表达，MTT和克隆形成实验检测细胞增殖，凋亡实验、刃天青细胞活力实验、western blot和荧光素酶报告基因实验检测蛋白表达，流式细胞术检测细胞周期。与相应的正常对照（NC）组织相比，在30个配对组织中，25个癌组织具有miR-21上调（25/30，83.8%）;此外，在8个HNC细胞系中，miR-21表达在三个中显著上调：UPCI-4 B、UMSCC-1和UPCI-15 B。在UMSC-I和UPCI-4 B细胞系中，miR-21模拟物增强了细胞增殖，减少了细胞凋亡并增加了存活力，而miR-21抑制剂导致了相反的效果（均P<0.001）;此外，miR-21直接靶向肿瘤抑制剂磷酸酶和张力蛋白同源物（PTEN）并抑制PTEN表达。此外，miR-21模拟物诱导顺铂耐药性，而miR-21抑制剂恢复顺铂敏感性。miR-21的过表达可通过抑制PTEN表达促进细胞增殖、减少细胞凋亡并诱导耐药。靶向miR-21可以促进癌症诊断，恢复药物敏感性，并提高治疗效果。
Drug resistance, either intrinsic or acquired, can impair treatment effects and result in increased cell motility and death. MicroRNA-21 (miR-21), a proto-oncogene, may facilitate the development or maintenance of drug resistance in cancer cells. Restoring drug sensitivity can improve therapeutic strategies, a possibility that requires functional evaluation and mechanistic exploration. For miR-21 detection, matched tissue samples from 30 head and neck squamous cell carcinoma (HNSCC) patients and 8 head and neck cancer (HNC) cell lines were obtained. Reverse transcription-PCR to detect expression, MTT and clonogenic assays to evaluate cell proliferation, apoptosis assays, resazurin cell viability assays, western blot and luciferase reporter assays to detect protein expression, and flow cytometry to analyse the cell cycle were adopted. Compared to the corresponding normal control (NC) tissues, 25 cancer tissues had miR-21 upregulation among the 30 matched pair tissues (25/30, 83.8%); furthermore, among the 8 HNC cell lines, miR-21 expression that was notably upregulated in three: UPCI-4B, UMSCC-1, and UPCI-15B. In both the UMSCC-1 and UPCI-4B cell lines, the miR-21 mimic enhanced cell proliferation with reduced apoptosis and increased viability, whereas the miR-21 inhibitor resulted in the opposite effects (all P<0.001); additionally, miR-21 directly targeted the tumour suppressor phosphatase and tensin homologue (PTEN) and inhibited PTEN expression. Furthermore, the miR-21 mimic induced cisplatin resistance, while the miR-21 inhibitor restored cisplatin sensitivity. Overexpression of miR-21 can enhance cell proliferation, reduce apoptosis, and induce drug resistance by inhibiting PTEN expression. Targeting miR-21 may facilitate cancer diagnosis, restore drug sensitivity, and improve therapeutic effects.
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影响因子：
5.2
作者：
Bhattacharyya T;Kainickal CT
通讯作者：
Kainickal CT
影响因子：
4.5
作者：
Cai, XZ;Hagedorn, CH;Cullen, BR
通讯作者：
Cullen, BR
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
DOI：
10.1158/1078-0432.ccr-13-2675
发表时间：
2014-02-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Mydlarz W;Uemura M;Ahn S;Hennessey P;Chang S;Demokan S;Sun W;Shao C;Bishop J;Krosting J;Mambo E;Westra W;Ha P;Sidransky D;Califano J
通讯作者：
Califano J
影响因子：
3.4
作者：
Huang, Yong;Yang, You Bing;Cheng, Xiang Chao
通讯作者：
Cheng, Xiang Chao