microRNA-365 inhibits YAP through TLR4-mediated IRF3 phosphorylation and thereby alleviates gastric precancerous lesions.
microRNA-365 inhibits YAP through TLR4-mediated IRF3 phosphorylation and thereby alleviates gastric precancerous lesions.
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microRNA-365通过TLR4介导的IRF3磷酸化抑制YAP从而减轻胃癌前病变
DOI：
10.1186/s12935-020-01578-0
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发表时间：
2020-11-13
影响因子：
5.8
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Zhang T;Zhang K;Ji K;Zhang C;Jiang Y;Zhang Q;Tian Z;Wang X;Zhang M;Li X
BackgroundGastric carcinoma (GC) is currently one of the most common malignant tumors of the digestive system, and gastric precancerous lesions play a vital role in studying the mechanism of GC. Multiple microRNAs (miRNAs) have been documented to be potential biomarkers to indicate progression of gastric precancerous lesions. In this study, we explained the anti-cancer effect of miR-365 in gastric precancerous lesions via regulation of the TLR4/IRF3/YAP/CDX2 axis.MethodsmiR-365, TLR4, CDX2 and IPF3 expression was determined in GC and atrophic gastritis tissues and cells. After transfection of shRNA and overexpression plasmids, in vitro experiments detected the alteration of cell viability, apoptosis and inflammatory factors. Bioinformatics analysis, Co-IP and dual luciferase reporter gene assay were conducted to evaluate the binding between miR-365 and TLR4 as well as IRF3 and YAP. Rat models were established to explore the effect of the miR-365 and TLR4 on gastric precancerous lesions.ResultsmiR-365 was poorly expressed in GC and atrophic gastritis tissues and GC cell lines, while TLR4, CDX2 and IRF3 were overexpressed. Of note, miR-365 was indicated to target TLR4 and thereby suppressed cancer progression and increased hemoglobin content. Interestingly, silencing of TLR4 was accompanied by decreased IRF3 phosphorylation and reduced expression with less binding between CDX2 and IRF3. Downregulation of YAP resulted in declined CDX2 expression in cancer cells. Moreover, the inhibitory role of miR-365 was further confirmed in animal models.ConclusionTaken together, miR-365-mediated TLR4 inhibition reduces IRF3 phosphorylation and YAP-mediated CDX2 transcription to impede progression of gastric precancerous lesions.
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影响因子：
6.1
作者：
Liu YQ;Bai ZG;Ma XM;Zhang ZT
通讯作者：
Zhang ZT
影响因子：
4.6
作者：
Kasurinen, Aaro;Hagstrom, Jaana;Haglund, Caj
通讯作者：
Haglund, Caj
DOI：
10.26355/eurrev_202005_21172
发表时间：
2020-05-01
影响因子：
3.3
作者：
Tong, L.;Han, W-Z;Zhuang, M.
通讯作者：
Zhuang, M.
miRNA在癌细胞和肿瘤微环境中的管制。
影响因子：
28.2
作者：
Rupaimoole R;Calin GA;Lopez-Berestein G;Sood AK
通讯作者：
Sood AK
影响因子：
--
作者：
Su, Qiang;Li, Lang;Zhao, Jinmin
通讯作者：
Zhao, Jinmin