Fang Y, Shen H, Cao Y, Li H, Qin R, Chen Q, Long L, Zhu X L, Xie C J, Xu W L
Department of Central Laboratory, The First Affiliated People's Hospital, Jiangsu University, ZhenjiangJiangsu, China, Department of Central Laboratory, The First Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China.
Department of Oncology, The First Affiliated People's Hospital, Jiangsu University, ZhenjiangJiangsu, China, Department of Oncology, The First Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China.
Braz J Med Biol Res. 2014 Jan;47(1):60-9. doi: 10.1590/1414-431X20133324. Epub 2014 Jan 10.
MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression implicated in cancer, which play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. The aim of this study was to investigate whether miR-30c mediated the resistance of breast cancer cells to the chemotherapeutic agent doxorubicin (ADR) by targeting tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ). miR-30c was downregulated in the doxorubicin-resistant human breast cancer cell lines MCF-7/ADR and MDA-MB-231/ADR compared with their parental MCF-7 and MDA-MB-231 cell lines, respectively. Furthermore, we observed that transfection of an miR-30c mimic significantly suppressed the ability of MCF-7/ADR to resist doxorubicin. Moreover, the anti-apoptotic gene YWHAZ was confirmed as a target of miR-30c by luciferase reporter assay, and further studies indicated that the mechanism for miR-30c on the sensitivity of breast cancer cells involved YWHAZ and its downstream p38 mitogen-activated protein kinase (p38MAPK) pathway. Together, our findings provided evidence that miR-30c was one of the important miRNAs in doxorubicin resistance by regulating YWHAZ in the breast cancer cell line MCF-7/ADR.
微小RNA（miRNA）是一类小RNA分子，可调节与癌症相关的基因表达，在发育、分化、凋亡和增殖等多种生物学过程中发挥关键作用。本研究旨在探讨miR-30c是否通过靶向酪氨酸3-单加氧酶/色氨酸5-单加氧酶激活蛋白ζ（YWHAZ）介导乳腺癌细胞对化疗药物阿霉素（ADR）的耐药性。与亲本MCF-7和MDA-MB-231细胞系相比，阿霉素耐药的人乳腺癌细胞系MCF-7/ADR和MDA-MB-231/ADR中miR-30c分别下调。此外，我们观察到转染miR-30c模拟物可显著抑制MCF-7/ADR抵抗阿霉素的能力。此外，荧光素酶报告基因检测证实抗凋亡基因YWHAZ是miR-30c的靶标，进一步研究表明miR-30c影响乳腺癌细胞敏感性的机制涉及YWHAZ及其下游的p38丝裂原活化蛋白激酶（p38MAPK）途径。总之，我们的研究结果表明，在乳腺癌细胞系MCF-7/ADR中，miR-30c通过调节YWHAZ成为阿霉素耐药中重要miRNA之一。
