Department of Oncology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China.
Int J Biol Sci. 2018 Feb 9;14(2):228-236. doi: 10.7150/ijbs.22849. eCollection 2018.
Breast cancer (BC) is the most common cause of death in women throughout the world. Although microRNAs (miRNAs) have been identified as novel regulators in carcinogenesis, there are still abundant hidden treasure needed to be excavated. In the present study, we found that miR-519d expression was remarkably decreased in both human BC tissues and MCF-7 cells. CCK8 and 5-Ethynyl-2'-deoxyuridine (EdU) assays were used to evaluate cell proliferation. Wound-healing and transwell assays were performed for detection of cell migration and invasion. The results demonstrated miR-519d overexpression dramatically suppressed MCF-7 cells proliferation, migration and invasion. While downregulation of miR-519d by miR-519d inhibitor substantially increased MCF-7 cell carcinogenesis. Further analysis identified Matrix Metalloproteinase-3 (MMP3) as a direct target of miR-519d. QRT-PCR and western blot results indicated the correlative expression of miR-519d and MMP3 in BC tissues and MCF-7 cells. In summary, our data uncovered the novel molecular interaction between miR-519d and MMP3, indicating a therapeutic strategy of miR-519d for BC.
乳腺癌(BC)是全世界女性死亡的最常见原因。尽管 microRNAs(miRNAs)已被鉴定为致癌作用中的新型调节剂,但仍有大量隐藏的宝藏有待挖掘。在本研究中,我们发现 miR-519d 在人乳腺癌组织和 MCF-7 细胞中表达明显降低。CCK8 和 5-乙炔基-2'-脱氧尿苷(EdU)测定用于评估细胞增殖。划痕愈合和 Transwell 测定用于检测细胞迁移和侵袭。结果表明 miR-519d 过表达可显著抑制 MCF-7 细胞增殖、迁移和侵袭。而 miR-519d 抑制剂下调 miR-519d 则显著增加 MCF-7 细胞的癌变。进一步分析鉴定出基质金属蛋白酶-3(MMP3)是 miR-519d 的直接靶标。QRT-PCR 和 Western blot 结果表明 miR-519d 和 MMP3 在 BC 组织和 MCF-7 细胞中的相关性表达。总之,我们的数据揭示了 miR-519d 和 MMP3 之间新的分子相互作用,表明 miR-519d 是治疗乳腺癌的一种策略。