Laboratorio de Biotecnología, Instituto de Ciencias Biomédicas, Universidad Autónoma de Ciudad Juárez, Ciudad Juárez, Chihuahua, México; The Cytometry, Screening and Imaging Core Facility, Border Biomedical Research Center, Department of Biological Sciences, the University of Texas at El Paso, El Paso, Texas, USA.
The Cytometry, Screening and Imaging Core Facility, Border Biomedical Research Center, Department of Biological Sciences, the University of Texas at El Paso, El Paso, Texas, USA.
Arch Med Res. 2018 Jul;49(5):323-334. doi: 10.1016/j.arcmed.2018.10.008. Epub 2018 Nov 3.
This study presents a prediction of putative miRNA within several Human Papillomavirus (HPV) types by using bioinformatics tools and a strategy based on sequence and structure alignment. Currently, little is known about HPV miRNAs.
Computational methods have been widely applied in the identification of novel miRNAs when analyzing genome sequences. Here, ten whole-genome sequences from HPV-6, -11, -16, -18, -31, -33, -35, -45, -52, and -58 were analyzed. Software based on local contiguous structure-sequence features and support vector machine (SVM), as well as additional bioinformatics tools, were utilized for identification and classification of real and pseudo microRNA precursors.
An initial analysis predicted 200 putative pre-miRNAs for all the ten HPV genome variants. To derive a smaller set of pre-miRNAs candidates, stringent validation criteria was conducted by applying <‒10 ΔG value (Gibbs Free Energy). Thus, only pre-miRNAs with total scores above the cut-off points of 90% were considered as putative pre-miRNAs. As a result of this strategy, 19 pre-miRNAs were selected (hpv-pre-miRNAs). These novel pre-miRNAs were located in different clusters within HPV genomes and some of them were positioned at splice regions. Additionally, the 19 identified pre-miRNAs sequences varied between HPV genotypes. Interestingly, the newly identified miRNAs, 297, 27b, 500, 501-5, and 509-3-5p, were closely implicated in carcinogenesis participating in cellular longevity, cell cycle, metastasis, apoptosis evasion, tissue invasion and cellular growth pathways.
The novel putative miRNAs candidates could be promising biomarkers of HPV infection and furthermore, could be targeted for potential therapeutic interventions in HPV-induced malignancies.
本研究通过生物信息学工具和基于序列和结构比对的策略，对几种人类乳头瘤病毒（HPV）类型中的推定 miRNA 进行预测。目前，对 HPV miRNA 知之甚少。
在分析基因组序列时，计算方法已广泛应用于新 miRNA 的鉴定。在这里，分析了 HPV-6、-11、-16、-18、-31、-33、-35、-45、-52 和 -58 的十个全基因组序列。基于局部连续结构-序列特征和支持向量机（SVM）的软件以及其他生物信息学工具，用于鉴定和分类真实和伪 microRNA 前体。
最初的分析预测了所有十种 HPV 基因组变体的 200 个推定 pre-miRNA。为了得出一个较小的 pre-miRNA 候选集，通过应用 <‒10 ΔG 值（吉布斯自由能）进行了严格的验证标准。因此，只有总得分高于 90%的截止点的 pre-miRNA 被认为是推定的 pre-miRNA。通过这种策略，选择了 19 个 pre-miRNA（hpv-pre-miRNA）。这些新的 pre-miRNA 位于 HPV 基因组中的不同簇中，其中一些位于剪接区。此外，鉴定出的 19 个 pre-miRNA 序列在 HPV 基因型之间存在差异。有趣的是，新鉴定的 miRNA，297、27b、500、501-5 和 509-3-5p，与癌症发生密切相关，参与细胞长寿、细胞周期、转移、凋亡逃逸、组织侵袭和细胞生长途径。
新的推定 miRNA 候选物可能是 HPV 感染的有前途的生物标志物，并且可以针对 HPV 诱导的恶性肿瘤进行潜在的治疗干预。
