Luo Long-Ji, Yang Fan, Ding Jia-Ji, Yan Da-Li, Wang Dan-Dan, Yang Su-Jin, Ding Li, Li Jian, Chen Dan, Ma Rong, Wu Jian-Zhong, Tang Jin-Hai
Xuzhou Medical University, Xuzhou 221004, China; Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing 210009, China.
The Forth Clinical School of Nanjing Medical University, Nanjing 210009, China.
Gene. 2016 Dec 5;594(1):47-58. doi: 10.1016/j.gene.2016.08.057. Epub 2016 Sep 1.
Metastasis is the leading cause of death among breast cancer (BCa) patients and triple negative breast cancer (TNBC) as one of BCa subtypes exhibits the worst survival rate due to its highly aggressive and metastatic behavior. A growing body of research has shown that the dynamic expression of microRNAs (miRNAs) was intimately associated with tumor invasion and metastasis. Recent studies have demonstrated miR-31 as a metastasis-suppressor in breast cancer, but it is still known little about the mechanism of it suppresses metastasis. The special AT-rich sequence-binding protein-2 (SATB2) has been reported to involve in tumor proliferation and invasion, but its function and relationship with miR-31 in breast cancer is still unknown. Here we found that the expression of miR-31 was downregulated in TNBC tissue and cell line. MiR-31 expression was increased after MDA-MB-231 cell was treated by 5-aza-2'-deoxycytidine (5-AZA-CdR), enhance the expression of miR-31 significantly inhibited MDA-MB-231 cell migration and invasion, downregulation of miR-31 expression could promoted MCF-7 cell migration and invasion. The expression of SATB2 was negatively correlated with miR-31 and was upregulated in MCF-7 and MDA-MB-231. Silencing SATB2 expression significantly inhibited MCF-7 and MDA-MB-231 cell proliferation, migration and invasion. Luciferase reporter assays indicated SATB2 is a direct target of miR-31. Taken together, these results suggest miR-31 inhibited TNBC cells migration and invasion through suppressing SATB2 expression.
转移是乳腺癌（BCa）患者死亡的主要原因，而三阴性乳腺癌（TNBC）作为BCa的一种亚型，因其高度侵袭性和转移性的行为，生存率最差。越来越多的研究表明，微小RNA（miRNA）的动态表达与肿瘤侵袭和转移密切相关。最近的研究表明miR-31是乳腺癌中的一种转移抑制因子，但其抑制转移的机制仍知之甚少。据报道，富含AT序列的特殊结合蛋白2（SATB2）参与肿瘤增殖和侵袭，但其在乳腺癌中的功能以及与miR-31的关系仍不清楚。在这里，我们发现miR-31在TNBC组织和细胞系中的表达下调。MDA-MB-231细胞经5-氮杂-2'-脱氧胞苷（5-AZA-CdR）处理后，miR-31表达增加，miR-31表达的增强显著抑制MDA-MB-231细胞的迁移和侵袭，miR-31表达的下调可促进MCF-7细胞的迁移和侵袭。SATB2的表达与miR-31呈负相关，在MCF-7和MDA-MB-231中上调。沉默SATB2表达可显著抑制MCF-7和MDA-MB-231细胞的增殖、迁移和侵袭。荧光素酶报告基因检测表明SATB2是miR-31的直接靶点。综上所述，这些结果表明miR-31通过抑制SATB2表达来抑制TNBC细胞的迁移和侵袭。
