Ma Fang, Feng Yeqian, Li Weihui, Li Zexuan, Liu Tiebang, Li Lingjiang
Mental Health Institute, The Second Xiangya Hospital, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan, Central South University, Changsha, Hunan 410011, P.R. China.
Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
Exp Ther Med. 2017 May;13(5):2515-2522. doi: 10.3892/etm.2017.4255. Epub 2017 Mar 22.
MicroRNAs (miRs) play critical roles in the development and malignant progression of human cancers. miR-148a has previously been found to inhibit the migration and invasion of breast cancer cells. However, the underlying mechanism of miR-148a in regulating the viability and migration of estrogen receptor (ER) α-positive breast cancer cells is still unknown. In this study, ERα-positive breast cancer MCF7 cells were treated with estradiol (E2). Data from MTT and wound healing assays showed that E2 treatment promoted the viability and migration of MCF7 cells. A bioinformatics analysis and luciferase reporter assay identified ERα as a direct target of miR-148a. Ectopic expression of miR-148a significantly decreased the protein expression of ERα (P<0.01), while knockdown of miR-148a significantly increased the ERα protein level in MCF7 cells (P<0.01). Furthermore, miR-148a overexpression significantly inhibited the E2-induced viability and migration of MCF7 cells (P<0.01), similar to the effect of silencing ERα. However, overexpression of ERα rescued the suppressed viability and migration caused by miR-148a upregulation. Finally, it was found that E2 treatment led to a significant decrease in the miR-148a level in MCF7 cells (P<0.01). These results suggest that miR-148a can suppress the E2-induced viability and migration of MCF7 breast cancer cells via inhibition of ERα protein expression, expanding the understanding of miR function in ERα-positive breast cancer.
微小RNA（miRs）在人类癌症的发生发展及恶性进展中发挥着关键作用。此前已发现miR - 148a可抑制乳腺癌细胞的迁移和侵袭。然而，miR - 148a调控雌激素受体（ER）α阳性乳腺癌细胞活力和迁移的潜在机制仍不清楚。在本研究中，用雌二醇（E2）处理ERα阳性乳腺癌MCF7细胞。MTT和伤口愈合试验数据显示，E2处理可促进MCF7细胞的活力和迁移。生物信息学分析和荧光素酶报告基因试验确定ERα是miR - 148a的直接靶点。miR - 148a的异位表达显著降低了ERα的蛋白表达（P<0.01），而敲低miR - 148a则显著增加了MCF7细胞中ERα蛋白水平（P<0.01）。此外，miR - 148a过表达显著抑制了E2诱导的MCF7细胞活力和迁移（P<0.01），类似于沉默ERα的效果。然而，ERα的过表达挽救了由miR - 148a上调导致的活力和迁移抑制。最后，发现E2处理导致MCF7细胞中miR - 148a水平显著降低（P<0.01）。这些结果表明，miR - 148a可通过抑制ERα蛋白表达来抑制E2诱导的MCF7乳腺癌细胞活力和迁移，拓展了对miR在ERα阳性乳腺癌中功能的认识。
