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

Abstract

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.

<p>Blocking circ_0000520 Suppressed Breast Cancer Cell Growth, Migration and Invasion Partially via miR-1296/SP1 Axis Both in vitro and in vivo</p>

“…Here, we intended to explore the biologic role of circ_0000520 in cell growth and metastasis of BCa, and to figure out the interaction of circ_0000520 , miR-1296 and specificity protein 1 (SP1), a basal transcriptional factor that widely regulates genes to contribute to the hallmarks of cancers including BCa. 15 , 16 …”

Gene expression analysis of human prostate cell lines with and without tumor metastasis suppressor CD82

“…Additionally, PC3-5 V, PC3–57, and PC3–29 are clonal cell lines derived from PC3. Discrepant results between PC3–57 + CD82 and PC3–29 + CD82 clonal cells when compared with PC3-5 V -CD82 cells may be due to the fact that prostate tumor can harbor multiple genetically distinct cancer clones with heterogenous ERG+, ETS+, SPI+ and triple negative subtypes [ 80 , 81 ] that can affect different gene regulation and pathways. Moreover, high vs. low metastatic cells have been known to be derived from parental PC3 cells [ 82 ].…”

Overexpression of SP1 restores autophagy to alleviate acute renal injury induced by ischemia-reperfusion through the miR-205/PTEN/Akt pathway

“…Increasing evidence suggests an interesting interaction between SP1 and micro-RNAs. In the study of prostate cancer, it was found that SP1 regulates the expression of miR-3178 and affects the metastasis of prostate cancer cells [18]. In esophageal squamous cell carcinoma, SP1 directly activates the expression of miR-205 to regulate the radiation sensitivity of cancer cells [19].…”