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长链非编码 RNA MAFG-AS1 通过调控 miR-339-5p/MMP15 促进乳腺癌的侵袭转移。

LncRNA MAFG-AS1 promotes the aggressiveness of breast carcinoma through regulating miR-339-5p/MMP15.

机构信息

Department of Obstetrics and Gynecology, Shandong Jiyang Public Hospital, Ji'nan, Shandong, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Apr;23(7):2838-2846. doi: 10.26355/eurrev_201904_17561.

DOI:10.26355/eurrev_201904_17561
PMID:31002134
Abstract

OBJECTIVE

The main purposes of this study are to investigate the possible effects of long noncoding RNAs (lncRNAs) MAFG-AS1 on the growth and metastasis of breast carcinoma.

PATIENTS AND METHODS

The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay was used to assess the MAFG-AS1 level in breast cancer tissues and cells. The wound healing and transwell invasion analysis were applied to explore the invasion and migration of breast cancer cell in vitro. The expressions of epithelial-mesenchymal transition (EMT) related markers were determined by Western blotting. Xenograft model and lung metastasis model were used to assess the progression of breast carcinoma cell in vivo.

RESULTS

The level of lncRNA MAFG-AS1 is higher in breast carcinoma, and the aggressive phenotypes of breast carcinoma cell are enhanced by MAFG-AS1 transfection. Moreover, we identify that MAFG-AS1 overexpression reduces the expression of miR-339-5p and miR-339-5p is the target of MAFG-AS1 in breast carcinoma. In addition, matrix metalloproteinase 15 (MMP15) is the functional regulated gene of miR-339-5p in breast carcinoma. The aggressiveness of breast carcinoma induced by lncRNA MAFG-AS1 is weakened by the miR-339-5p. Finally, we demonstrated that the development of breast carcinoma cell is enhanced by MAFG-AS1 in vivo.

CONCLUSIONS

MAFG-AS1 appears to play an oncogene role in breast carcinoma by regulating the miR-339-5p/MMP15.

摘要

目的

本研究的主要目的是探讨长链非编码 RNA(lncRNA)MAFG-AS1 对乳腺癌生长和转移的可能影响。

患者和方法

采用实时定量聚合酶链反应(qRT-PCR)检测乳腺癌组织和细胞中 MAFG-AS1 的水平。采用划痕愈合和 Transwell 侵袭分析体外研究乳腺癌细胞的侵袭和迁移。Western blot 检测上皮间质转化(EMT)相关标志物的表达。利用异种移植模型和肺转移模型评估乳腺癌细胞在体内的进展。

结果

lncRNA MAFG-AS1 在乳腺癌中高表达,MAFG-AS1 转染可增强乳腺癌细胞的侵袭和迁移能力。此外,我们发现 MAFG-AS1 过表达降低了 miR-339-5p 的表达,而 miR-339-5p 是乳腺癌中 MAFG-AS1 的靶基因。此外,基质金属蛋白酶 15(MMP15)是 miR-339-5p 在乳腺癌中的功能调节基因。miR-339-5p 可减弱 lncRNA MAFG-AS1 诱导的乳腺癌侵袭性。最后,我们证实 MAFG-AS1 可在体内增强乳腺癌细胞的发展。

结论

MAFG-AS1 通过调节 miR-339-5p/MMP15 ,在乳腺癌中发挥癌基因作用。

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