Rahimi-Moghaddam Akram, Ghorbanmehr Nassim, Gharbi Sedigheh, Nili Fatemeh, Korsching Eberhard
Department of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran.
Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.
Biochem Genet. 2024 Jun 7. doi: 10.1007/s10528-024-10837-y.
Human papillomavirus accounts for 99.7% of all cervical cancer cases worldwide. The viral oncoproteins alter normal cell signaling and gene expression, resulting in loss of cell cycle control and cancer development. Also, microRNAs (miRNAs) have been reported to play a critical role in cervical carcinogenesis. Especially these are not only appropriate targets for therapeutic intervention in cervical cancer but also early diagnostic signals. The given study tries to improve the sparse knowledge on miRNAs and their role in this physiological context. Deregulated miRNAs were identified by analyzing the raw data of the well-founded GSE20592 dataset including 16 tumor/normal pairs of human cervical tissue samples. The dataset was quantified by a conservative strategy based on HTSeq and Salmon, followed by target prediction via TargetScan and miRDB. The comprehensive pathway analysis of all factors was performed using DAVID. The theoretical results were subject of a stringent experimental validation in a well-characterized clinical cohort of 30 tumor/normal pairs of cervical samples. The top 31 miRNAs and their 140 primary target genes were closely intertwined with the PI3K-Akt signaling pathway. MiR-21-3p and miR-1-3p showed a prominent regulatory role while miR-542, miR-126, miR-143, and miR-26b are directly targeting both PI3K and AKT. This study provides insights into the regulation of PI3K-Akt signaling as an important inducer of cervical cancer and identified miR-542, miR-126, miR-143, and miR-26b as promising inhibitors of the PI3K-Akt action.
人乳头瘤病毒占全球所有宫颈癌病例的99.7%。病毒癌蛋白会改变正常细胞信号传导和基因表达，导致细胞周期控制丧失和癌症发展。此外，据报道，微小RNA（miRNA）在宫颈癌发生过程中起关键作用。尤其是这些不仅是宫颈癌治疗干预的合适靶点，也是早期诊断信号。本研究试图改善关于miRNA及其在这种生理背景下作用的稀少知识。通过分析可靠的GSE20592数据集的原始数据来鉴定失调的miRNA，该数据集包括16对人宫颈组织样本的肿瘤/正常样本。该数据集通过基于HTSeq和Salmon的保守策略进行定量，随后通过TargetScan和miRDB进行靶标预测。使用DAVID对所有因素进行综合通路分析。理论结果在一个具有30对肿瘤/正常宫颈样本的特征明确的临床队列中进行了严格的实验验证。排名前31的miRNA及其140个主要靶基因与PI3K-Akt信号通路密切相关。MiR-21-3p和miR-1-3p发挥了突出的调节作用，而miR-542、miR-126、miR-143和miR-26b直接靶向PI3K和AKT。本研究深入了解了PI3K-Akt信号传导作为宫颈癌重要诱导因子的调节机制，并确定miR-542、miR-126、miR-143和miR-26b是PI3K-Akt作用的有前景的抑制剂。
