INTERPLAY OF EPIGENETIC REGULATION OF KI-67 AND P53 BY MIR-21 AND MIR-34A IN CERVICAL INTRAEPITHELIAL NEOPLASIA

Cervical cancer (CC), primarily linked to persistent HPV infection, arises from complex genetic and epigenetic alterations. The early detection of cervical intraepithelial neoplasia (CIN) allows for CC prevention. Recent data highlights the importance of epigenetic biomarkers, including non-coding RNAs such as miR-21 and miR-34a. Our aim was to investigate the interplay between Ki-67 and p53 expression and their epigenetic regulation by miR-21 and miR-34a to better predict the course of CIN.

Tumor biopsies from 50 patients with CIN 1-3/HSIL were analyzed. We performed immunohistochemical analysis of Ki-67 and p53 expression and qRT-PCR for the analysis of miRNA expression.

The average miR-21 and miR-34a levels were 5.8 ± 2.8 and 1.42 ± 0.85 (a.u.), respectively, while Ki-67 and p53 averaged 136.9 ± 79.9 and 93.15 ± 49.5 H-score points. Positive correlations were found between miR-21 and Ki-67 (r = 0.76) and miR-34a and p53 expressions (r = 0.65). Tumors with low Ki-67 showed 2.48-fold lower miR-21 levels, and low p53 tumors showed 4.2-fold lower miR-34a levels. While no correlation with age or menstrual status was found, miR-21 (r = 0.78), Ki-67 (r = 0.68), and miR-34a (r = -0.59) correlated with CIN grading (p < 0.05). The miR-21 and Ki-67 levels increased in CIN 2 and CIN 3 compared to CIN 1 in both HPV-positive and HPV-negative samples. The miR-34a levels were the lowest in CIN 3 HPV-negative samples and significantly decreased with CIN progression in HPV-positive samples. The p53 levels were significantly higher in CIN 3 cases of both the HPV-positive and HPV-negative groups.

Our study demonstrates that the miR‑21, miR-34a, Ki-67, and p53 expression levels are significantly correlated with each other and are distinctly associated with the progression of CIN grades and HPV status, highlighting their potential as crucial CC biomarkers.