miR-26b enhances the sensitivity of hepatocellular carcinoma to Doxorubicin via USP9X-dependent degradation of p53 and regulation of autophagy.
miR-26b enhances the sensitivity of hepatocellular carcinoma to Doxorubicin via USP9X-dependent degradation of p53 and regulation of autophagy.
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miR-26b通过USP9X依赖性p53降解和自噬调节增强肝细胞癌对阿霉素的敏感性
DOI：
10.7150/ijbs.52517
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发表时间：
2021
影响因子：
9.2
通讯作者：
Liang T
中科院分区：
文献类型：
--
作者：
Chen E;Li E;Liu H;Zhou Y;Wen L;Wang J;Wang Y;Ye L;Liang T
多药耐药是肝细胞癌（HCC）治疗面临的主要挑战，而microRNA（miRNA）表达的过表达或缺失与各种细胞系的耐药特性密切相关。然而，潜在的分子机制仍不清楚。CCK-8、EdU、流式细胞术和透射电子显微镜分别用于确定细胞活力、增殖、凋亡、自噬流和纳米颗粒表征。在这项研究中，结果表明，miR-26 b的表达下调后，阿霉素治疗的人肝癌组织。miR-26 b模拟物增强了HCC细胞对阿霉素的敏感性，除了在Hep 3B细胞中不存在p53。蛋白酶体抑制剂MG 132的递送逆转了多柔比星处理后miR-26 b对p53水平的抑制作用。Tenovin-1（MDM 2抑制剂）仅在具有野生型p53的HepG 2细胞中保护p53免于泛素化介导的降解。当用miR-26 b模拟物转染时，Tenovin-1预处理增强HCC细胞对阿霉素的抗性。此外，miR-26 b模拟物抑制阿霉素诱导的自噬，自噬诱导剂雷帕霉素消除了miR-26 b药物敏感性效应的差异。在体内，用sp 94 dr/miR-26 b模拟纳米颗粒加多柔比星治疗抑制肿瘤生长。我们目前的数据表明，miR-26 b通过减少由DNA损伤药物和自噬调节引起的USP 9 X介导的p53去泛素化来增强HCC细胞对阿霉素的敏感性。这种调节HCC的miRNA介导的途径将有助于开发新的治疗策略。
Multi-drug resistance is a major challenge to hepatocellular carcinoma (HCC) treatment, and the over-expression or deletion of microRNA (miRNA) expression is closely related to the drug-resistant properties of various cell lines. However, the underlying molecular mechanisms remain unclear. CCK-8, EdU, flow cytometry, and transmission electron microscopy were performed to determine cell viability, proliferation, apoptosis, autophagic flow, and nanoparticle characterization, respectively. In this study, the results showed that the expression of miR-26b was downregulated following doxorubicin treatment in human HCC tissues. An miR-26b mimic enhanced HCC cell doxorubicin sensitivity, except in the absence of p53 in Hep3B cells. Delivery of the proteasome inhibitor, MG132, reversed the inhibitory effect of miR-26b on the level of p53 following doxorubicin treatment. Tenovin-1 (an MDM2 inhibitor) protected p53 from ubiquitination-mediated degradation only in HepG2 cells with wild type p53. Tenovin-1 pretreatment enhanced HCC cell resistance to doxorubicin when transfected with an miR-26b mimic. Moreover, the miR-26b mimic inhibited doxorubicin-induced autophagy and the autophagy inducer, rapamycin, eliminated the differences in the drug sensitivity effect of miR-26b. In vivo, treatment with sp94dr/miR-26b mimic nanoparticles plus doxorubicin inhibited tumor growth. Our current data indicate that miR-26b enhances HCC cell sensitivity to doxorubicin through diminishing USP9X-mediated p53 de-ubiquitination caused by DNA damaging drugs and autophagy regulation. This miRNA-mediated pathway that modulates HCC will help develop novel therapeutic strategies.
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影响因子：
4.2
作者：
Liu J;Xing Y;Rong L
通讯作者：
Rong L
嵌合肽缩合超分子纳米颗粒递送 miR-212 增强胰腺导管腺癌对阿霉素的敏感性
影响因子：
14
作者：
Chen, Wei;Zhou, Yue;Liang, Tingbo
通讯作者：
Liang, Tingbo
DOI：
10.1016/j.bbrc.2018.03.215
发表时间：
2018-05-15
影响因子：
3.1
作者：
Chen, Hui;Yang, Fan;Wang, Lu-Wen
通讯作者：
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影响因子：
5.2
作者：
Huang, Haijin;Tang, Jie;Zhang, Xiaoyu
通讯作者：
Zhang, Xiaoyu
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影响因子：
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作者：
Lin J;Zhang L;Huang H;Huang Y;Huang L;Wang J;Huang S;He L;Zhou Y;Jia W;Yun J;Luo R;Zheng M
通讯作者：
Zheng M