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Sp1 Suppresses MiR-3178 to Promote Metastasis Invasion Cascade via Upregulation of TRIOBP
Molecular Therapy - Nucleic Acids ( IF 8.8 ) Pub Date : 2018-04-26
Hui Wang, Kai Li, Yu Mei, Xuemei Huang, Zhenglin Li, Qingzhu Yang, Huanjie Yang

Specificity protein (Sp1) plays an important role in invasion-metastasis cascade. Sp1 regulation on protein coding genes have been extensively investigated, however little is known about its regulation on protein non-coding genes. In this study, miR-3178 is reported as a novel target of Sp1 in multiple cancer cell models. Sp1 functions as its transcriptional suppressor as evidenced by luciferase reporter and ChIP assays. In line with the pro-metastatic role of Sp1, miR-3178 exerts anti-metastasis function. Overexpression of miR-3178 inhibits both migration and invasion of highly metastatic prostate, lung and breast cancer cells while antagonizing miR-3178 promotes those events in their lowly metastatic counterparts. In vivo study demonstrates that miR-3178 suppresses the tail vein inoculated prostate cancer cells to form colonies in lung, lymph node and liver of BALB/c nude mice. MiR-3178 directly targets the 3' UTR of TRIOBP-1 and TRIOBP-5, the two isoforms of TRIOBP expressed in prostate, lung and breast cancer cells. Furthermore, overexpression of TRIOBP-1 could rescue miR-3178 inhibition on cell migration and invasion. Collectively, our findings reveal the regulatory axis of Sp1/miR-3178/TRIOBP in metastasis cascade. Our results suggest miR-3178 as a promising application to suppress metastasis in Sp1 overexpressed cancers.



中文翻译:

Sp1抑制MiR-3178通过上调TRIOBP促进转移侵袭级联

特异性蛋白(Sp1)在侵袭转移级联中起重要作用。Sp1对蛋白质编码基因的调控已被广泛研究,但是对于其对蛋白质非编码基因的调控知之甚少。在这项研究中,miR-3178被报道为多种癌细胞模型中Sp1的新靶标。Sp1发挥其转录抑制作用,如荧光素酶报告基因和ChIP分析所证明。与Sp1的促转移作用一致,miR-3178发挥抗转移功能。miR-3178的过表达抑制高度转移的前列腺癌,肺癌和乳腺癌细胞的迁移和侵袭,而拮抗miR-3178则促进其低转移对应物的这些事件。体内研究表明,miR-3178抑制了尾巴接种的前列腺癌细胞在BALB / c裸鼠的肺,淋巴结和肝脏中形成集落。MiR-3178直接靶向TRIOBP-1和TRIOBP-5的3'UTR,TRIOBP-1和TRIOBP-5在前列腺,肺癌和乳腺癌细胞中表达的TRIOBP的两种同工型。此外,TRIOBP-1的过表达可以挽救miR-3178对细胞迁移和侵袭的抑制作用。总的来说,我们的发现揭示了Sp1 / miR-3178 / TRIOBP在转移级联反应中的调控轴。我们的结果表明,miR-3178作为抑制Sp1过表达癌症转移的一种有前途的应用。

更新日期:2018-04-26
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