Analyses of the international human genome sequencing results in 2004 converged to a consensual number of ~20,000 protein-coding genes, spanning over <2% of the total genomic sequence. Therefore, the developmental and physiological complexity of human beings remains unaccounted if viewed only in terms of the number of protein-coding genes; the epigenetic influences involving chromatin remodelling and RNA interference and alternative precursor messenger RNA splicing of functional protein-coding transcripts as well as post-translational modifications of proteins increase the diversity and the functionality of the proteome and likely explain the increased complexity. In addition, there has been an explosion of research addressing possible functional roles for the other 98% of the human genome that does not encode proteins. In fact, >90% of the human genome is likely to be transcribed yielding a complex network of overlapping transcripts that include tens of thousands of long RNAs with little or no protein forming capacity; they are collectively called non-coding RNA. This review highlights the fundamental concepts of biological roles of non-coding RNA and their importance in regulation of cellular physiology under disease conditions like cancer.

Aptamers are short sequences of nucleic acid (DNA or RNA) or peptide molecules which adopt a conformation and bind cognate ligands with high affinity and specificity in a manner akin to antibody-antigen interactions. It has been globally acknowledged that aptamers promise a plethora of diagnostic and therapeutic applications. Although use of nucleic acid aptamers as targeted therapeutics or mediators of targeted drug delivery is a relatively new avenue of research, one aptamer-based drug “Macugen” is FDA approved and a series of aptamer-based drugs are in clinical pipelines. The present review discusses the aspects of design, unique properties, applications, and development of different aptamers to aid in cancer diagnosis, prevention, and/or treatment under defined conditions.

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Human telomerase reverse transcriptase is an essential rate-limiting component of telomerase complex. hTERT protein in association with other proteins and the human telomerase RNA (hTR) shows telomerase activity, essential for maintaining genomic integrity in proliferating cells. hTERT binds hTR through a decapeptide located in the RID2 (RNA interactive domain 2) domain of N-terminal region. Since hTERT is essential for telomerase activity, inhibitors of hTERT are of great interest as potential anti-cancer agent. We have selected RNA aptamers against a synthetic peptide from the RID2 domain of hTERT by employing in vitro selection protocol (SELEX). The selected RNAs could bind the free peptide, as CD spectra suggested conformational change in aptamer upon RID2 binding. Extracts of cultured breast cancer cells (MCF7) expressing this aptamer showed lower telomerase activity as estimated by TRAP assay. hTERT-binding RNA aptamers hold promise as probable anti-cancer therapeutic agent.

Treatment of cholera still is a global challenge for health authorities across the world. It is important to use effective antimicrobials for curbing cholera and shortens the duration of illness. As per the WHO recommendations, ciprofloxacin and doxycycline are drugs of choice to be used in treatment of severe cholera. Single doses of ciprofloxacin have been reported to be better than single dose of doxycycline in eradication of cholera bacterium from stool. Earlier we have reported that reduced susceptibility or resistance to fluoroquinolones in Vibrio cholerae O1 is associated with either delay or failure in cholera treatment. V. cholerae harbours two related type II topoisomerases, which alter DNA topology through a DNA cleavage complex. Fluoroquinolones stabilizing the DNA breakage‐reunion complex inhibit DNA replication. Point mutations in gyraseA and ParC responsible for reduced susceptibility to fluoroquinolones are well known. Here, we discuss the QnrVC mediated acquired mechanism of resistance in epidemic strains of V. cholerae. PCR analyses and DNA sequencing revealed presence of qnrVC gene (encoding QnrVC) in epidemic V. cholerae O1 in strains from central and Eastern parts of India. Higher order structural analyses confirmed that QnrVC exhibits right‐handed quadrilateral beta‐helical fold. The shape, size, and charge distribution on QnrVC is reminiscent of a 30‐bp long B‐form DNA. Docking studies revealed that it occupies the entire length of the G segment DNA binding site of type II topoisomerases, thus interfering with fluoroqunolone action. Strains harbouring the qnrVC elements were either resistant or less susceptible to ciprofloxacin as per CLSI, 2010 USA guidelines. Cloning of qnrVC in E. coli transformant mediated 4‐8 folds increment of MIC for ciprofloxacin. The use fluoroquinolones in cholera cases should be closely monitored and development of alternate chemotherapeutic agents targetting transition type II topoisomerases should be given due priority. Grant Funding Source: UGC, DBT and DST, Govt. of India