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微小RNA-30a通过靶向E-钙黏蛋白和锌指E盒结合同源异型盒2抑制黑色素瘤肿瘤转移。

miR-30a Inhibits Melanoma Tumor Metastasis by Targeting the E-cadherin and Zinc Finger E-box Binding Homeobox 2.

作者信息

Noori Jahangir, Sharifi Mohammadreza, Haghjooy Javanmard Shaghayegh

机构信息

Applied Physiology Research Center, Cardiovascular Research Institute, Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Adv Biomed Res. 2018 Nov 27;7:143. doi: 10.4103/abr.abr_146_18. eCollection 2018.

Abstract

BACKGROUND

Epithelial-mesenchymal transition (EMT) is actively involved in tumor invasion. The main hallmark of EMT is downregulation of the adherens junction protein E-cadherin due to transcriptional repression. Candidate E-cadherin transcription repressors are members of ZEB family, ZEB2 belong to the ZEB family transcription factor that is pivotal for embryonic development and tumor progression. ZEB2 (zinc finger E-box binding homeobox 2) is most widely known as an inducer of EMT. Growing evidence have shown the involvement of microRNAs in cancer progression. In this study, we demonstrate that miR-30a is a potent suppressor of melanoma metastasis to the lung.

MATERIALS AND METHODS

In this study, miR-30a has been transfected into B16-F10 melanoma cells, and then cells were injected intravenously into C57BL/6 mice. Then, the mice were sacrificed and nodules in the lungs were enumerated.

RESULTS

Ectopic expression of miR-30a in melanoma cell line resulted in the suppression of pulmonary metastasis. We also found that transfected miR-30a into melanoma cells could increase E-cadherin and decrease ZEB2 expression.

CONCLUSIONS

Our findings showed that increased expression of miR-30a in melanoma inhibited metastasis by targeting ZEB2 and E-cadherin.

摘要

背景

上皮-间质转化(EMT)积极参与肿瘤侵袭。EMT的主要标志是由于转录抑制导致黏附连接蛋白E-钙黏蛋白下调。E-钙黏蛋白转录抑制因子的候选者是ZEB家族成员,ZEB2属于ZEB家族转录因子,对胚胎发育和肿瘤进展至关重要。ZEB2(锌指E盒结合同源框2)最为人所知的是作为EMT的诱导因子。越来越多的证据表明微小RNA参与癌症进展。在本研究中,我们证明miR-30a是黑色素瘤肺转移的有效抑制因子。

材料与方法

在本研究中,将miR-30a转染到B16-F10黑色素瘤细胞中,然后将细胞静脉注射到C57BL/6小鼠体内。随后,处死小鼠并计数肺内结节。

结果

miR-30a在黑色素瘤细胞系中的异位表达导致肺转移受到抑制。我们还发现将miR-30a转染到黑色素瘤细胞中可增加E-钙黏蛋白表达并降低ZEB2表达。

结论

我们的研究结果表明,黑色素瘤中miR-30a表达增加通过靶向ZEB2和E-钙黏蛋白抑制转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4168/6282499/6865f5a9b63c/ABR-7-143-g002.jpg

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