Substantial fraction of high-quality information is continuously being added into the existing pool of knowledge related to the biology of telomeres. Based on the insights gleaned from decades of research, it is clear that chromosomal stability needs a highly controlled and dynamic balance of DNA gain and loss in each terminal tract of telomeric repeats. Telomeres are formed by tandem repeats of TTAGGG sequences, which are gradually lost with each round of division of the cells. Targeted inhibition of telomerase to effectively induce apoptosis in cancer cells has attracted tremendous attention and overwhelmingly increasingly list of telomerase inhibitors truthfully advocates pharmacological significance of telomerase. Telomerase reverse transcriptase (TERT) is a multi-talented and catalytically active component of the telomerase-associated protein machinery. Different proteins of telomerase-associated machinery work in a synchronized and orchestrated manner to ensure proper maintenance of telomeric length of chromosomes. Rapidly emerging scientific findings about regulation of TERT by microRNAs has revolutionized our understanding related to the biology of telomeres and telomerase. In this review, we have comprehensively discussed how different miRNAs regulate TERT in different cancers. Use of miRNA-based therapeutics against TERT in different cancers needs detailed research in preclinical models for effective translation of laboratory findings to clinically effective therapeutics.

Fagonia cretica L. is a tropical plant of family Zygophyllaceae with wide range of medicinally important secondary metabolites. The low cellular uptake of the polar compounds in the extract of the plant limits its biological application. In present study efficacy of F. cretica modified bioactive nano-formulations for in vitro modulation of TRAIL mediated extrinsic apoptotic pathway as cancer therapy was investigated. F. cretica methanolic extracts were formulated at nano-scale for green synthesis of silver nanoparticles, albumin conjugation and liposomes encapsulation to enhance targeted bioactivity against cancer. Physical characterization of the synthesized nanoparticles was done by SEM, EDX and Zeta potential analyzer. In vitro cell viability assay MTT was done for MCF-7, Hep-2, HUH-7 and HCEC cell lines. Relative expression variation of the apoptotic pathway-associated genes was done by qRT-PCR. SEM revealed spherical shape of 56.62 ± 8.04, 143 ± 11.54 and 83.36 ± 38.73 nm size and zeta potential − 18.6, − 15.5 and − 18.3 mV for liposomes, silver and albumin nanoparticles. Silver nanoparticles showed highest anticancer activity in vitro than albumin and liposomes nanoparticles with IC₅₀ 0.101 ± 0.004, 0.177 ± 0.03 and 0.434 ± 0.022 mg/mL in MCF-7, Hep-2 and HUH-7 respectively. F. cretica albumin and silver nanoparticles upregulated the in vitro TRAIL, DR4, DR5 and FADD gene expression at statistically significant levels in Hep-2 cell lines. Nano-formulations of F. cretica proved therapeutically important biomolecules in vitro. The hypothesized modulation of extrinsic apoptosis pathway genes through the plant nanoparticles proved novel medicinal options for effective treatment of cancer and enhancing the bioavailability of the active plant metabolites.

Thyroid cancer (TC) is caused by genetic factors and or their cross talk with lifestyle and environment. An important role of miRNA involvement has been identified in different human diseases alongside the cancer. The growing cloud of miRNA discoveries narrates miRNA-221 and miRNA-222 as key elements of ready arsenal in the cancer micro-niches. The aim of present study was to identify the variations of miRNA-221 and miRNA-222 expression in TC tissues and their likely association with TC. miRNA-221 and miRNA-222 were investigated for their expressional alterations in TC tissue samples and healthy thyroid tissue. Expression of miRNA-221 and -222 was analyzed through real time PCR. The relative gene expression of both the miRNA was quantified and statistically evaluated. miRNA-221 and miRNA-222 were found to be highly over expressed when compared with samples of multinodular goiter (MNG) and normal controls. Interestingly, it was also noted that miRNA-221 and miRNA-222 expression is working in a cluster in thyroid cancer patients. So, it can be concluded that the expressional alterations of miRNA-221 and -222 are playing their potential role in the development of thyroid cancer.

Background: Rationale: The miRNAs are short non-coding functional RNAs that are involved in the regulation of transcriptomes. It was found that human miRNA-146a and miRNA34b/c are important microRNAs and are functioning either as onco-miRNAs, or acting as tumor suppressors, in different conditions. To date, no study has been performed to evaluate the alterations of miRNA-146ars2910164 and miRNA34b/crs4938723 polymorphism as a risk factor in the development of thyroid cancer in the Pakistani population. Mutational analysis of rs2910164 and rs4938723 of miRNA-146a and miRNA-34b/c was carried out to check their association with the development of thyroid carcinogenesis. Material and Methods: Papillary thyroid cancer (PTC) patients with age and gender-matched controls were recruited for the present study. DNA extraction, genotyping of rs2910164 and rs4938723 was carried out by ARMS-PCR. Statistical analyses were carried out using SPSS software (version 20). Results: The odds ratio for risk allele C of rs2910164 for patients and controls was 23.0168 (3.0321–174.7208) with a p-value of <0.0001, showing that the frequency of the major allele G was lower in patients while the frequency of minor allele C was higher in patients. Similarly, the odds ratio for risk allele C of rs4938723 was 1.8621 (1.0321–3.3596) with a p-value of <0.03788 showing significant association with the development of thyroid cancer. Conclusions: The study highlights the significant association of miRNAs SNPs as one of the genetic risk factor for PTC. It was concluded that miRNA-146a (rs2910164) showed higher frequency of minor allele C in patients. Similarly in miRNA-34b/c gene SNP rs4938723 was observed to have a strong association with the development of thyroid cancer as the frequency of rare allele C was higher in patients.