Custódio Dias Duarte Bruna, Ribeiro Queiroz Fábio, Percínio Costa Álvaro, Borges de Melo Neto Angelo, Pereira de Souza Melo Carolina, de Oliveira Salles Paulo Guilherme, de Jesus Jeremias Wander, Lima Bertarini Pedro Luiz, Rodrigues do Amaral Laurence, da Conceição Braga Letícia, de Souza Gomes Matheus, Lopes da Silva Filho Agnaldo
Laboratório de Bioinformática e Análises Moleculares, Universidade Federal de Uberlândia, 38702-178, Patos de Minas, MG, Brazil.
Laboratório de Pesquisa Translacional Em Oncologia, Instituto Mário Penna, 30380-490, Belo Horizonte, MG, Brazil.
Noncoding RNA Res. 2024 Oct 24;11:104-114. doi: 10.1016/j.ncrna.2024.10.004. eCollection 2025 Apr.
Cervical cancer (CC) is a global public health concern, primarily caused by persistent infection with oncogenic types of human papillomavirus (HPV). The World Health Organization (WHO) has established a plan to eliminate CC as a public health issue by the year 2100. However, the implementation of the HPV vaccine is impeded by vaccine restrictions and misinformation despite its demonstrated effectiveness. The CC treatment is influenced by the disease stage, with an unfavorable prognosis for those in advanced stages. This study aimed to investigate the potential of long non-coding RNAs (lncRNAs) in CC by identifying and characterizing related lncRNAs, elucidating their regulatory mechanisms and molecular interactions, and analyzing their expression patterns in patients with diverse responses to chemoradiotherapy. Non-stem cells from CC were isolated using flow cytometry sorting and used for total RNA extraction. The RNA was used to build libraries that were subsequently sequenced using the Illumina Nextseq 550.417 lncRNAs that showed differentially expressed between CC patients who responded or not to treatment. Further analysis demonstrated that these lncRNAs significantly interact with several molecules, which play crucial roles in CC progression and therapeutic resistance. Statistical analysis correlated the expression profile of these lncRNAs with treatment efficacy. Three lncRNAs, , , and , were identified with positive expression related to non-response to chemoradiotherapy and worse progression-free survival in CC patients. Specifically, lncRNA has its up-regulation related to non-response and down-regulation to response to chemoradiotherapy treatment.
宫颈癌(CC)是一个全球公共卫生问题,主要由致癌型人乳头瘤病毒(HPV)的持续感染引起。世界卫生组织(WHO)已制定计划,到2100年将宫颈癌作为一个公共卫生问题消除。然而,尽管HPV疫苗已证明有效,但其实施仍受到疫苗限制和错误信息的阻碍。宫颈癌的治疗受疾病阶段影响,晚期患者预后不佳。本研究旨在通过鉴定和表征相关长链非编码RNA(lncRNA)、阐明其调控机制和分子相互作用以及分析其在对放化疗有不同反应的患者中的表达模式,来研究lncRNA在宫颈癌中的潜力。使用流式细胞术分选从宫颈癌中分离出非干细胞,并用于总RNA提取。该RNA用于构建文库,随后使用Illumina Nextseq 550进行测序。在对治疗有反应或无反应的宫颈癌患者之间,有417种lncRNA表现出差异表达。进一步分析表明,这些lncRNA与几种分子显著相互作用,这些分子在宫颈癌进展和治疗耐药中起关键作用。统计分析将这些lncRNA的表达谱与治疗效果相关联。鉴定出三种lncRNA,即 、 和 ,其阳性表达与宫颈癌患者对放化疗无反应及无进展生存期较差相关。具体而言,lncRNA 的上调与无反应相关,而下调与对放化疗治疗的反应相关。