Tornesello Maria Lina, Faraonio Raffaella, Buonaguro Luigi, Annunziata Clorinda, Starita Noemy, Cerasuolo Andrea, Pezzuto Francesca, Tornesello Anna Lucia, Buonaguro Franco Maria
Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Naples, Italy.
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
Front Oncol. 2020 Feb 20;10:150. doi: 10.3389/fonc.2020.00150. eCollection 2020.
Prolonged infection of uterine cervix epithelium with human papillomavirus (HPV) and constitutive expression of viral oncogenes have been recognized as the main cause of the complex molecular changes leading to transformation of cervical epithelial cells. Deregulated expression of microRNAs (miRNA), long non-coding RNAs (lncRNA), and circular RNAs (circRNA) is involved in the initiation and promotion processes of cervical cancer development. Expression profiling of small RNAs in cervical neoplasia revealed up-regulated "oncogenic" miRNAs, such as miR-10a, miR-21, miR-19, and miR-146a, and down regulated "tumor suppressive" miRNAs, including miR-29a, miR-372, miR-214, and miR-218, associated with cell growth, malignant transformation, cell migration, and invasion. Also several lncRNAs, comprising among others HOTAIR, MALAT1, GAS5, and MEG3, have shown to be associated with various pathogenic processes such as tumor progression, invasion as well as therapeutic resistance and emerged as new diagnostic and prognostic biomarkers in cervical cancer. Moreover, human genes encoded circular RNAs, such as has_circ-0018289, have shown to sponge specific miRNAs and to concur to the deregulation of target genes. Viral encoded circE7 has also demonstrated to overexpress E7 oncoprotein thus contributing to cell transformation. In this review, we summarize current literature on the complex interplay between miRNAs, lncRNAs, and circRNAs and their role in cervical neoplasia.
人乳头瘤病毒（HPV）对子宫颈上皮细胞的长期感染以及病毒癌基因的组成型表达已被认为是导致宫颈上皮细胞转化的复杂分子变化的主要原因。微小RNA（miRNA）、长链非编码RNA（lncRNA）和环状RNA（circRNA）的表达失调参与了宫颈癌发生发展的起始和促进过程。宫颈肿瘤中微小RNA的表达谱分析显示，“致癌性”miRNA如miR-10a、miR-21、miR-19和miR-146a上调，而“肿瘤抑制性”miRNA如miR-29a、miR-372、miR-214和miR-218下调，这些miRNA与细胞生长、恶性转化、细胞迁移和侵袭相关。此外，包括HOTAIR、MALAT1、GAS5和MEG3等在内的几种lncRNA已显示与肿瘤进展、侵袭以及治疗耐药性等各种致病过程相关，并成为宫颈癌新的诊断和预后生物标志物。而且，人类基因编码的环状RNA，如has_circ-0018289，已显示可吸附特定的miRNA并参与靶基因的失调。病毒编码的circE7也已证明可过表达E7癌蛋白，从而促进细胞转化。在本综述中，我们总结了关于miRNA、lncRNA和circRNA之间复杂相互作用及其在宫颈肿瘤中的作用的当前文献。
