Alimohammadi Mina, Fooladi Abbas Ali Imani, Mafi Alireza, Alavioun Seyedeh Mana, Cho William C, Reiter Russel J, Khormizi Fateme Zare, Yousefi Tooba, Farahani Najma, Khoshnazar Seyedeh Mahdieh, Hushmandi Kiavash
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Transl Oncol. 2025 May;55:102363. doi: 10.1016/j.tranon.2025.102363. Epub 2025 Mar 22.
Cervical cancer (CC) is the primary cause of cancer-related mortality among women in developing countries and is the most prevalent disease linked to human papillomavirus (HPV). Over 70 % of CC cases result from persistent infections with high-risk HPV types. The virus typically targets the mucocutaneous epithelium, generating viral particles in mature epithelial cells, which leads to disruptions in normal cell-cycle regulation and promotes uncontrolled cellular proliferation. This unchecked cell division results in the accumulation of genetic damage, contributing to the pathogenesis of CC. While HPV infection is a key etiological factor, the disease's progression also necessitates the involvement of genetic and epigenetic influences. One of the epigenetic regulators, long noncoding RNAs (lncRNAs), are characterized by transcripts exceeding 200 nucleotides. These molecules play crucial roles in various cellular processes, including transcription regulation, RNA metaboli35 per 100,000sm, and apoptosis. Investigating the specific roles of lncRNAs in modulating gene expression related to the oncogenic mechanisms of CC, particularly in the context of high-risk HPV infections, may provide valuable insights for diagnostic and therapeutic advancements. Herein, we first review key molecular mechanisms by which lncRNAs interfere with CC-related HPV development. Then, diagnostic, prognostic, and therapeutic potentials of these lncRNA molecules will be highlighted in depth. The focus of this article is on the role of lncRNAs associated with HPV-related CC, emphasizing the investigation of signaling pathways and their underlying molecular mechanisms. Furthermore, we explore the therapeutic potential and diagnostic relevance of the most significant lncRNAs in the context of CC, thereby highlighting their importance in advancing treatment strategies and improving patient outcomes.
宫颈癌(CC)是发展中国家女性癌症相关死亡的主要原因,也是与人类乳头瘤病毒(HPV)相关的最常见疾病。超过70%的宫颈癌病例是由高危型HPV的持续感染引起的。该病毒通常靶向黏膜上皮,在成熟上皮细胞中产生病毒颗粒,这会导致正常细胞周期调控的破坏,并促进细胞的不受控制增殖。这种不受控制的细胞分裂导致遗传损伤的积累,促成了宫颈癌的发病机制。虽然HPV感染是一个关键的病因,但该疾病的进展还需要遗传和表观遗传因素的参与。表观遗传调节因子之一,长链非编码RNA(lncRNA),其特征是转录本超过200个核苷酸。这些分子在各种细胞过程中发挥关键作用,包括转录调控、RNA代谢和细胞凋亡。研究lncRNA在调节与宫颈癌致癌机制相关的基因表达中的具体作用,特别是在高危HPV感染的背景下,可能为诊断和治疗进展提供有价值的见解。在此,我们首先综述lncRNA干扰与宫颈癌相关的HPV发展的关键分子机制。然后,将深入强调这些lncRNA分子的诊断、预后和治疗潜力。本文的重点是与HPV相关的宫颈癌的lncRNA的作用,强调对信号通路及其潜在分子机制的研究。此外,我们在宫颈癌的背景下探索最显著的lncRNA的治疗潜力和诊断相关性,从而突出它们在推进治疗策略和改善患者预后方面的重要性。