Shen Y, Ye Y F, Ruan L W, Bao L, Wu M W, Zhou Y
Shaoxing Women & Children's Hospital, Shaoxing, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Genet Mol Res. 2017 Feb 23;16(1):gmr-16-01-gmr.16019479. doi: 10.4238/gmr16019479.
Breast cancer, which derives from the epithelium of the mammary glands, is one of the most common cancers diagnosed in women globally. To date, the authors of many studies have reported that the deregulation of microRNAs (miRNAs) plays a crucial role in the occurrence, development, and metastasis of tumors. Here, we discovered that miR-660-5p was upregulated in the breast cancer cell lines MCF7 and MDA-MB-231 compared with that in the normal control cell line CCD-1095Sk. We then inhibited the expression of miR-660-5p to investigate its biological function in cancer development, progression, and metastasis. We determined the changes in the levels of expression of transcription factor CP2 (TFCP2) and CDKN1A to further clarify the specific mechanism involved. The results showed that downregulation of miR-660-5p significantly suppressed the proliferation, migration, and invasion of MCF7 breast cancer cell. Moreover, inhibition of miR-660-5p promoted cell cycle G1 arrest and reduced apoptosis in breast cancer cells. The specific mechanism studies confirmed that TFCP2 was a direct downstream target of miR-660-5p. Aberrant expression of miR-660-5p repressed TFCP2 expression, whereas inhibition of miR-660-5p decreased TFCP2 protein expression, which is a vital factor in the downstream signaling pathway. In conclusion, miR-660-5p can regulate the proliferation, migration, and invasion of human breast cancer cells, and is a novel potential therapeutic target for the clinical treatment of breast cancer.
乳腺癌起源于乳腺上皮，是全球女性中最常见的诊断癌症之一。迄今为止，许多研究的作者报告称，微小RNA（miRNA）的失调在肿瘤的发生、发展和转移中起着关键作用。在这里，我们发现与正常对照细胞系CCD-1095Sk相比，miR-660-5p在乳腺癌细胞系MCF7和MDA-MB-231中上调。然后我们抑制miR-660-5p的表达，以研究其在癌症发展、进展和转移中的生物学功能。我们测定了转录因子CP2（TFCP2）和CDKN1A表达水平的变化，以进一步阐明其中涉及的具体机制。结果表明，miR-660-5p的下调显著抑制了MCF7乳腺癌细胞的增殖、迁移和侵袭。此外，抑制miR-660-5p可促进细胞周期G1期阻滞并减少乳腺癌细胞的凋亡。具体机制研究证实，TFCP2是miR-660-5p的直接下游靶点。miR-660-5p的异常表达抑制了TFCP2的表达，而抑制miR-660-5p则降低了TFCP2蛋白的表达，TFCP2是下游信号通路中的一个重要因子。总之，miR-660-5p可以调节人乳腺癌细胞的增殖、迁移和侵袭，是乳腺癌临床治疗的一个新的潜在治疗靶点。
