Sp1 Suppresses miR-3178 to Promote the Metastasis Invasion Cascade via Upregulation of TRIOBP

作者：Wang, Hui; Li, Kai; Mei, Yu; Huang, Xuemei; Li, Zhenglin; Yang, Qingzhu; Yang, Huanjie^*

来源：Molecular Therapy - Nucleic Acids, 2018, 12: 1-11.

DOI：10.1016/j.omtn.2018.04.008

• EPITHELIAL-MESENCHYMAL TRANSITION
• COLORECTAL-CANCER PROGRESSION
• ACTIN BINDING-PROTEIN
• HEPATOCELLULAR-CARCINOMA
• TRANSCRIPTION FACTOR
• PANCREATIC-CANCER
• CELL-LINE
• EXPRESSION
• GROWTH
• MICRORNAS

Specificity protein (Sp1) plays an important role in invasion-metastasis cascade. Sp1 regulation on protein coding genes has 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 chromatin immunoprecipitation (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 whereas antagonizing miR-3178 promotes those events in their lowly metastatic counterparts. The 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, two isoforms of TRIOBP expressed in prostate, lung, and breast cancer cells. 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.

• 出版日期2018-9-7
• 单位哈尔滨工业大学