Abstract 49P
Background
Genetic and epigenetic changes have been shown to be crucial regulators in cervical cancer progression. However, the mechanisms and role of miRNA dysregulation in cervical carcinogenesis are still not clear. We aimed to evaluate four miRNAs (miR-130a-3p, miR-205-5p, miR-4531, and miR-381-3p) and the regulation of their targets in human cervical cancer (CC) cell lines.
Methods
We used a panel of CC cell lines including five commercial cell lines (HeLa, SiHa, CasKi, C4-I, and C-33A) and one primary cell line (HCB-514) established in our laboratory. Primary Epidermal Keratinocytes cell line (HaCaT) was used as control. The differential expression level of miRNAs was assessed by quantitative PCR analysis. Gene expression profile analysis was performed using nCounter PanCancer Pathways panel (NanoString Technologies®) to compare HCB-514 and HaCaT cell lines. The interaction networks of the miRNA-targets were constructed by the Cytoscape program and REACTOME FI plug-in with the CC category.
Results
We found that miR-130a-3p was overexpressed in all CC cell lines and miR-205-5p was upregulated in CasKi, C4-IA, C-33A and HCB-514, both with a ≤2 fold-change. However, miR-4531 showed no difference between expression levels in CC cell lines compared to HaCaT cells. On the other hand, miR-381-3p was downregulated only in the HCB-514 cell line. We identified 14 differentially expressed genes: eight downregulated (WNT10A, ITGA2, BMP7, DLL1, PPP2R2B, SOX9, BMP4, and DUSP6) and six upregulated (LTBP1, TMPRSS2, RASAL1, PAX8, IL6R, and TLRB2) in the HCB-514 cell line compared to the HaCaT cell line. In the miRNA-target interaction analysis, we verified that WNT10A can be being silenced by upregulation of miR-130a-3p and miR-205-5p.
Conclusions
This study revealed that miR-130a-3p and miR-205-5p are upregulated in CC cell lines. WNT expression was predicted as a specific target of both upregulated miRNAs (miR-130a-3p and miR-205-5p). These results may be useful to better understand CC progression and the role of these microRNAs in this process.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer), Fundação de Amparo ao Pesquisador (FAPESP), and Researcher Aid and Incentive Program at the Barretos Cancer Hospital.
Disclosure
All authors have declared no conflicts of interest.