China
Africa
Explore chapters and articles related to this topic
Landscape of Papillomavirus in Human Cancers
Published in Satya Prakash Gupta, Cancer-Causing Viruses and Their Inhibitors, 2014
Susri Ray Chaudhuri (Guha), Anirban Roy, Indranil Chatterjee, Rahul Roy Chowdhury, Snehasikta Swarnakar
Recent studies showed that host cellular micro-RNAs (miRNAs) modulate expression of several viral genes resulting in perturbation of the host–pathogen interaction network. Likewise, viruses also encode miRNAs that interfere with the host miRNA pathway and that help them to protect themselves from host immune response (Reshmi and Pillai 2008). In contrast to general miRNAs, aberrant miR- NAs oppose the pathophysiologic outcome in accordance with their targeted miR- NAs. Disruption of miRNA expression correlates with hematopoietic malignancies (Zhao et al. 2013) as well as breast (Iorio et al. 2005), ovarian (Iorio et al. 2007), cervical (Lee et al. 2008), prostate (Tong et al. 2009), colorectal (Motoyama et al. 2009), gastric (Katada et al. 2009), nasopharyngeal (Chen et al. 2009), lung (Ortholan et al. 2009), and renal cancers (Petillo et al. 2009); miRNA expression profiles in cervical cancer cell lines showed that miR-24, miR-27a, and miR-205 were most abundant in frank cervical cancer. Downregulation of miR-34a, to which p53 binds and triggers cell proliferation, is a signature of HPV-induced cervical carcinogenesis (Wang et al. 2009). HPV-16 DNA-positive cervical cancer tissues showed downregulation of miR-23b that regulates urokinase-type plasminogen activator expression. In addition, downregulation of miR-218 and miR-203 are also noticed in HPV-16 DNA- integrated cervical cancer cell lines (Martinez et al. 2008). Experimental results on changes in miRNA expression during chemotherapy and radiotherapy raise hope of using miRNA as a therapeutic agent for HPV-related disorders. On the other hand, miRNA signature might be a potential prognostic marker for cervical cancer (Lee et al. 2008). Further experiments on miRNA transgenic and knock-out models are needed regarding safety and efficacy of miRNA therapy for cervical or head and neck cancers. In this line, use of locked nucleic acid (LAN)-modified oligonucleotides, anti miRNA oligonucleotides (AMOs), is in the infancy stages of evaluation for their therapeutic potency in cancers other than cervical cancer (Wu et al. 2006). Nonetheless, miRNA-based prognosis and therapeutics are welcomed for successful treatment of HPV-related cancers.
Advances in the discovery of microRNA-based anticancer therapeutics: latest tools and developments
Published in Expert Opinion on Drug Discovery, 2020
Kenneth K.W. To, Winnie Fong, Christy W.S. Tong, Mingxia Wu, Wei Yan, William C.S. Cho
ASOs are single strands of nucleic acid, typically 20–25 bases long, which were first used to inhibit mRNA targets. They bind with high affinity and specificity to their nucleic acid targets via Watson and Crick base-pairing. For the modulation of miRNA activity, ASOs interact complementarily with mature miRNAs and prevent their binding to the target mRNA [35]. To further increase the therapeutic potential of these ASOs, a number of modifications including (i) structural changes to the sugar backbone (2ʹO-methyl, 2ʹ-fluoro, 2ʹO-metoxyethyl, locked nucleic acids and peptide nucleic acids), and (ii) chemical modifications to the phosphodiester bonds (phosphorothioate, and N-mesyl and methoxyethyl-phosphoramidate) have been developed [36–39]. These structural modifications to the ASOs make them more resistance to nuclease-mediated degradation [36,39] and enhance their binding affinity to the target mRNAs [37] and penetration across the cell membrane [36,38]. Recently, Lima et al. reported a comprehensive guide for designing anti-miRNA oligonucleotides [40].