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

A Svintsitska, N Lygyrda, V Svintsitskyi, T Borikun, A Kryzhanivska
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引用次数: 0

Abstract

Background: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

背景:宫颈癌(CC)主要与持续性HPV感染有关,由复杂的遗传和表观遗传改变引起。早期发现宫颈上皮内瘤变(CIN)可以预防CC。最近的数据强调了表观遗传生物标志物的重要性,包括非编码rna,如miR-21和miR-34a。我们的目的是研究Ki-67和p53表达之间的相互作用以及miR-21和miR-34a对它们的表观遗传调控,以更好地预测CIN的病程。材料与方法:对50例CIN 1-3/HSIL患者的肿瘤活检进行分析。我们对Ki-67和p53的表达进行免疫组化分析,并对miRNA的表达进行qRT-PCR分析。结果:miR-21和miR-34a的平均水平分别为5.8±2.8和1.42±0.85 (a.u), Ki-67和p53的平均水平分别为136.9±79.9和93.15±49.5 h评分点。miR-21与Ki-67表达呈正相关(r = 0.76), miR-34a与p53表达呈正相关(r = 0.65)。低Ki-67肿瘤miR-21水平降低2.48倍,低p53肿瘤miR-34a水平降低4.2倍。miR-21 (r = 0.78)、Ki-67 (r = 0.68)和miR-34a (r = -0.59)与CIN分级相关(p < 0.05)。在hpv阳性和hpv阴性样本中,CIN 2和CIN 3中miR-21和Ki-67水平均高于CIN 1。miR-34a水平在CIN 3 hpv阴性样本中最低,在hpv阳性样本中随着CIN的进展而显著降低。hpv阳性组和hpv阴性组CIN 3病例中p53水平均显著升高。结论:我们的研究表明miR- 21、miR-34a、Ki-67和p53的表达水平彼此显著相关,并且与CIN分级和HPV状态的进展明显相关,突出了它们作为关键CC生物标志物的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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