Upregulation of microRNA-129-5p inhibits cell invasion, migration and tumor angiogenesis by inhibiting ZIC2 via downregulation of the Hedgehog signaling pathway in cervical cancer

Cancer Biol Ther. 2018;19(12):1162-1173. doi: 10.1080/15384047.2018.1491497. Epub 2018 Sep 27.

Abstract

Recently, some studies have placed additional research focus on microRNAs (miRNAs) in a bid to discover novel therapeutic approaches for cervical cancer (CC), which is one of the most common female reproductive tract malignancies with high rates of morbidity and mortality. Hence, the aim of the present study was to evaluate the ability of miR-129-5p to influence cell angiogenesis, invasion and migration by targeting ZIC2 through the Hedgehog signaling pathway in CC. Both CC and adjacent normal tissues were extracted from 87 eligible participating patients with CC. Measurements of the levels of miR-129-5p, mRNA and protein levels of ZIC2, sonic Hedgehog (Shh), Gli1, and Gli2 and levels of CXCL1, VEGF and Ang2 were determined accordingly. An angiogenesis assay was performed to evaluate cell angiogenesis in vitro, while a scratch test and transwell assay were adopted for cell invasion and migration determination. Lastly, tumor formation within nude mice was performed in order to analyze angiogenesis and tumor growth among the nude mice in vivo. The findings revealed that upregulation of miR-129-5p resulted in the decrease in the mRNA and protein levels of ZIC2, Shh, Gli1, Gli2, as well as reduced levels of CXCL1, VEGF and Ang2. Moreover, up-regulation of miR-129-5p was determined to inhibit CC cell angiogenesis ability in vitro, in addition to the processes of cell migration, and invasion. Finally, up-regulation of miR-129-5p was observed to inhibit the tumor growth and angiogenesis ability of nude mice in vivo. The results of the present study provided evidence suggesting that overexpressed miR-129-5p prevents angiogenesis and inhibits cell migration and invasion by means of negatively targeting ZIC2 through suppression of the Hedgehog signaling pathway in CC. Thus, highlighting the promise of miR-129-5p as a novel target for treating CC is promising.

Keywords: Hedgehog signaling pathway; Invasion; Migration; MircoRNA-129-5p; ZIC2; angiogenesis; cervical cancer.

Grant support

None.