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撤回:微小RNA-145调控肿瘤抑制候选基因3和丝裂原活化蛋白激酶通路以抑制结直肠癌进展。

Retracted: microRNA-145 regulates tumor suppressor candidate 3 and mitogen-activated protein kinase pathway to inhibit the progression of colorectal cancer.

作者信息

Tang Hanqing, Li Keming, Zheng Jianyu, Dou Xibin, Zhao Yufeng, Wang Luyao

机构信息

Department of Basic Medicine, Youjiang Medical University for Nationalities, Guangxi, China.

出版信息

J Cell Biochem. 2019 May;120(5):8376-8384. doi: 10.1002/jcb.28122. Epub 2018 Nov 28.

Abstract

BACKGROUND

It has been reported that microRNA-145 (miR-145) is downregulated in various cancers, including colorectal cancer (CRC). However, the role of miR-145 in progress of CRC and its mechanism remains unclear.

METHODS

The expressions of miR-145 and tumor suppressor candidate 3 (TUSC3) were determined in CRC tissues and cells by real-time quantitative polymerase chain reaction and Western blot analysis. The effects of miR-145 and TUSC3 on cell viability, migration, and invasion of CRC cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-trtrazolium bromide assay and trans-well chamber experiment, respectively. The interaction between miR-145 and TUSC3 was explored by bioinformatics analysis, luciferase reporter assay, and Western blot analysis. The abundances of mitogen-activated protein kinase (MAPK) signaling pathway-related proteins were measured by Western blot analysis.

RESULTS

miR-145 expression was downregulated in CRC tissues and cell lines, and TUSC3 was upregulated in CRC tissues and correlated inversely with miR-145 abundance. Overexpression of miR-145 and knockdown of TUSC3 suppressed cell viability, migration, and invasion in LS174T and HCT116 cells. Moreover, TUSC3 was indicated as a novel target of miR-145 and its expression was negatively regulated by miR-145. Restoration of TUSC3 can partially reverse the inhibitory effects of miR-145 on phosphorylation of extracellular signal-regulated kinases 1 and 2 in CRC cells.

CONCLUSION

miR-145 can inhibit the viability, migration, and invasion through addressing MAPK signaling pathway by targeting TUSC3 in CRC cells, providing a novel biomarker for treatment of CRC.

摘要

背景

据报道,微小RNA-145(miR-145)在包括结直肠癌(CRC)在内的多种癌症中表达下调。然而,miR-145在CRC进展中的作用及其机制仍不清楚。

方法

通过实时定量聚合酶链反应和蛋白质印迹分析测定CRC组织和细胞中miR-145和肿瘤抑制候选基因3(TUSC3)的表达。分别采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐法和Transwell小室实验检测miR-145和TUSC3对CRC细胞活力、迁移和侵袭的影响。通过生物信息学分析、荧光素酶报告基因检测和蛋白质印迹分析探索miR-145与TUSC3之间的相互作用。通过蛋白质印迹分析测定丝裂原活化蛋白激酶(MAPK)信号通路相关蛋白的丰度。

结果

miR-145在CRC组织和细胞系中表达下调,TUSC3在CRC组织中上调,且与miR-145丰度呈负相关。miR-145的过表达和TUSC3的敲低抑制了LS174T和HCT116细胞的活力、迁移和侵袭。此外,TUSC3被确定为miR-145的一个新靶点,其表达受miR-145负调控。TUSC3的恢复可部分逆转miR-145对CRC细胞中细胞外信号调节激酶1和2磷酸化的抑制作用。

结论

miR-145可通过靶向TUSC3调控MAPK信号通路来抑制CRC细胞的活力、迁移和侵袭,为CRC治疗提供了一种新的生物标志物。

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