MiR-218-5p, MiR-124-3p and MiR-23b-3p Act Synergistically to Modulate the Expression of NACC1, Proliferation, and Apoptosis in C-33A and CaSki Cells

Background: In cervical cancer (CC), miR-218-5p, -124-3p, and -23b-3p act as tumor suppressors. These miRNAs have specific and common target genes that modulate apoptosis, proliferation, invasion, and migration; biological processes involved in cancer.

Methods: miR-218-5p, -124-3p, and -23b-3p mimics were transfected into C-33A and CaSki cells, and RT-qPCR was used to quantify the level of each miRNA and . Proliferation was assessed by BrdU and apoptosis by Annexin V/PI. In the TCGA and The Human Protein Atlas databases, the level of mRNA and protein (putative target of the three miRNAs) was analyzed in CC and normal tissue. The relationship of NACC1 with the overall survival in CC was analyzed in GEPIA2. mRNA and protein levels were higher in CC tissues compared with cervical tissue without injury.

Results: An increased expression of NACC1 was associated with lower overall survival in CC patients. The levels of miR-218-5p, -124-3p, and -23b-3p were lower, and NACC1 was higher in C-33A and CaSki cells compared to HaCaT cells. The increase of miR-218-5p, -124-3p, and -23b-3p induced a significant decrease in mRNA. The transfection of the three miRNAs together caused more drastic changes in the level of , in the proliferation, and in the apoptosis with respect to the individual transfections of each miRNA.

Conclusion: The results indicate that miR-218-5p, -124-3p, and -23b-3p act synergistically to decrease NACC1 expression and proliferation while promoting apoptosis in C-33A and CaSki cells. The levels of , miR-218-5p, -124-3p, and -23b-3p may be a potential prognostic indicator in CC.