MicroRNAs in Cancer: Diagnostics and Therapeutics

Tumor initiation, recurrence, progression, and spread of cancer are multistep processes which involve numerous molecular and cellular mechanisms. One of the important regulators of the cancer-associated genes’ functions is identified as microRNA (miRNA) and is recently gaining much attention in the past decades. The miRNAs are highly conserved single-stranded noncoding RNAs containing 21–24 nucleotides and can posttranscriptionally regulate the expression of genes by silencing the target mRNAs. Recent evidences highlight the role of dysregulated miRNAs in human malignancies. Amplification or deletion of miRNA genes, abnormal activity of transcription factors, epigenetic modification, defects in the genes participating in the miRNA biogenesis pathway, and reduced level of intracellular miRNA due to presence of competitive endogenous RNAs (ceRNAs) are the primary mechanisms/reasons for miRNA dysregulation in diverse neoplasms. Genome-wide profiling of the differential expressions of miRNA signatures (miRNome) allows accurate discrimination of cancers of different tissues of origin. Continued development of miRNA classifiers aids benefits in tumor classification, diagnosis, and prognosis. Ability of miRNAs to activate tumor suppressor and repress oncogenic gene functions across drug-resistant/tumorigenic pathways provides a strong rationale for developing miRNA-based cancer therapeutics. Owing to the ability of miRNAs to activate tumor suppressor and repress oncogenic gene functions across drug-resistant/tumorigenic pathways, the present chapter further discusses the miRNA-based cancer therapeutics. Commonly employed strategies to target miRNAs with abnormal functions based on the use of oligonucleotides or virus-based constructs to either suppress the expression of oncogenic miRNAs or to reintroduce the lost tumor suppressor miRNAs in cancer cells. Nevertheless, chemical modifications to prevent miRNA degradation, effective and stable delivery of miRNAs to less-accessible target organs/tissues, and evaluation of possible side effects/risks associated with delivery systems are the few important issues need to be addressed to improve the therapeutic response of miRNAs.