Abstract
ABSTRACTRecently, 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.
Highlights
As a female-specific primary malignancy, cervical cancer (CC) that generally arises in the uterine cervix was accompanied by a high rate of morbidity and mortality.[1]
The findings indicated that decreased miR-129-5p, increased zinc finger protein of the cerebellum 2 (ZIC2), and activated Hedgehog signaling pathway in CC tissues
Results of the dual-luciferase reporter assay (Figure 3B) revealed that in comparison to the negative control (NC) group, luciferase activity of ZIC2 wild type (WT) 3ʹ-UTR was markedly inhibited by miR-1295p (p < 0.05) while no significant difference was detected in regard to ZIC2 MUT 3ʹ-UTR (p > 0.05)
Summary
As a female-specific primary malignancy, cervical cancer (CC) that generally arises in the uterine cervix was accompanied by a high rate of morbidity and mortality.[1]. CC ranks second regarding cancer-related deaths globally, with statistics estimating there to be as many as 474,000 female-deaths due to the disease by the year of 2030.3 a clinical statistics report indicated there to be 61,691 cases of CC in China, with 29,526 confirmed deaths, of which both figures represented 10% of cases globally.[4]. Current existing treatments are limited to, surgical procedures, radiotherapy, and chemotherapy which are generally applied in clinical settings, with largely poor outcomes due to metastasis.[5]. The situation may be more severe in China due to the size of the population, being so large that distinct variation in regard to wealth and medical resources between different regions.[4]. It is of great importance that new potential regimens are developed, in order to improve the outcomes of this deadly disease
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