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微小RNA-143靶向丝裂原活化蛋白激酶3以调控人乳腺癌细胞的增殖和骨转移。

MicroRNA-143 targets MAPK3 to regulate the proliferation and bone metastasis of human breast cancer cells.

作者信息

Du Yiqun, Zhang Jian, Meng Yanchun, Huang Mingzhu, Yan Wangjun, Wu Zhiqiang

机构信息

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.

Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

出版信息

AMB Express. 2020 Jul 31;10(1):134. doi: 10.1186/s13568-020-01072-w.

Abstract

MicroRNAs (miRs) have shown tremendous potential to act as therapeutic targets for cancer treatment. In this context, the present study was designed to investigate the potential of miR-143 in the treatment of breast cancer. Results showed that miR-143 to be significantly (P < 0.05) downregulated in breast cancer tissues and cell lines. The miR-143 has inhibitory effect on CAMA-1cell growth which was manifested as significant (P < 0.05) decline in loss of viability of cancer cells. The loss of cell viability was revealed to be due to the induction of apoptotic cell death as evident from acridine orange/ethidium bromide (AO/EB) and 4',6-diamidino-2-phenylindole (DAPI) staining assays. The apoptotic cell percentage was found to be 35.7% in miR-143 mimics transfected in comparison to 6.4% in miR-NC transfected cells. The western blot analysis showed that miR-143 caused enhancement in Bax and suppression in Bcl-2 expression in CAMA-1 cells. The miR-143 also suppressed the bone metastasis of the CAMA-1 cells by suppressing the expression of Jag1 and deactivation of the Rho-signalling pathway. The transwell assays also showed considerable anti-metastatic effects of miR-143 on CAMA-1 cells. Taken together, miR-143 has growth inhibitory anti-metastatic effect on breast cancer and thus may prove beneficial in breast cancer treatment.

摘要

微小RNA(miRs)已显示出作为癌症治疗靶点的巨大潜力。在此背景下,本研究旨在探讨miR - 143在乳腺癌治疗中的潜力。结果显示,miR - 143在乳腺癌组织和细胞系中显著下调(P < 0.05)。miR - 143对CAMA - 1细胞生长具有抑制作用,表现为癌细胞活力丧失显著(P < 0.05)下降。从吖啶橙/溴化乙锭(AO/EB)和4',6 - 二脒基 - 2 - 苯基吲哚(DAPI)染色试验可明显看出,细胞活力丧失是由于凋亡性细胞死亡的诱导。与转染miR - NC的细胞相比,转染miR - 143模拟物的细胞凋亡率为35.7%,而转染miR - NC的细胞凋亡率为6.4%。蛋白质印迹分析表明,miR - 143导致CAMA - 1细胞中Bax表达增强,Bcl - 2表达受到抑制。miR - 143还通过抑制Jag1的表达和Rho信号通路的失活来抑制CAMA - 1细胞的骨转移。Transwell试验也显示了miR - 143对CAMA - 1细胞具有显著的抗转移作用。综上所述,miR - 143对乳腺癌具有生长抑制和抗转移作用,因此可能对乳腺癌治疗有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bae0/7394972/48572f07a423/13568_2020_1072_Fig1_HTML.jpg

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