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微小RNA-155通过靶向丝裂原活化蛋白激酶7调控人乳腺癌的增殖和转移。

MicroRNA-155regulates the proliferation and metastasis of human breast cancers by targeting MAPK7.

作者信息

Liu Jian-Hua, Yang Yong, Song Qi, Li Jie Bao

机构信息

Department of Breast and Thyroid Surgery, Wuhan No.1 Hospital(Wuhan Chinese and Western Medicine Hospital),Wuhan,Hubei,430022,China.

出版信息

J BUON. 2019 May-Jun;24(3):1075-1080.

Abstract

PURPOSE

Breast cancer causes significant mortality in women world over. The lack of efficient and reliable biomarkers and therapeutic targets impedes the treatment of breast cancer. Herein, the role and therapeutic potential of miR-155 was investigated in different breast cancer cell lines Methods: Cell viability was determined by WST-1 and colony formation assays. Transfections were performed by Lipofectamine 2000 reagent. Cell cycle analysis was carried out by flow cytometry and apoptosis was detected by AO (acridine orange)/EB (ethidium bromide) staining. Cell migration and cell invasion were determined by wound healing assay. RNA and protein expressions were determined by qRT-PCR and western blotting, respectively.

RESULTS

miR-155 was significantly upregulated in all the breast cancer cells. Suppression of miR-155 in SK-BR-3 cells inhibited the growth and colony formation. The inhibition of SK-BR-3 cell proliferation was found to trigger apoptotic cell death and cell cycle arrest. Induction of apoptosis was also accompanied with enhancement of cytochrome c, Bax caspase 3, 8 and 9and inhibition of Bcl-2. Besides, suppression of miR-155 resulted in the decrease of cell migration and invasion. Bioinformatic analysis revealed MAPK7 to be the potential target of miR-155. The MAPK7 expression was also upregulated in all the breast cancer cells and suppression of miR-155 resulted in its downregulation.

CONCLUSION

Taken together, miR-155 may prove essential in the management of breast cancer.

摘要

目的

乳腺癌在全球女性中导致了显著的死亡率。缺乏高效可靠的生物标志物和治疗靶点阻碍了乳腺癌的治疗。在此,研究了miR-155在不同乳腺癌细胞系中的作用和治疗潜力。方法:通过WST-1和集落形成试验测定细胞活力。采用Lipofectamine 2000试剂进行转染。通过流式细胞术进行细胞周期分析,通过吖啶橙/溴化乙锭染色检测细胞凋亡。通过伤口愈合试验测定细胞迁移和侵袭。分别通过qRT-PCR和蛋白质印迹法测定RNA和蛋白质表达。

结果

miR-155在所有乳腺癌细胞中均显著上调。抑制SK-BR-3细胞中的miR-155可抑制其生长和集落形成。发现抑制SK-BR-3细胞增殖会引发凋亡性细胞死亡和细胞周期停滞。细胞凋亡的诱导还伴随着细胞色素c、Bax、半胱天冬酶3、8和9的增加以及Bcl-2的抑制。此外,抑制miR-155导致细胞迁移和侵袭减少。生物信息学分析显示MAPK7是miR-155的潜在靶点。MAPK7表达在所有乳腺癌细胞中也上调,抑制miR-155导致其下调。

结论

综上所述miR-155可能在乳腺癌的治疗中至关重要。

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