MicroRNA-663 antagonizes apoptosis antagonizing transcription factor to induce apoptosis in epithelial cells.

MicroRNAs are small functional RNAs that modulate various biological processes in cells by interfering with gene translation. We have previously demonstrated that certain miRNAs play a crucial role in the innate immune responses of human oral epithelial cells to Porphyromonas gingivalis. While addressing the mechanisms of P. gingivalis induced apoptosis in these cells, we discovered that certain miRNAs are upregulated upon stimulation with live bacteria. These upregulated miRNAs include hsa-miR-584, hsa-miR-572, hsa-miR-210, hsa-miR-492, hsa-miR-623 and hsa-miR-663. Further analysis revealed an unexpected role for hsa-miR-663 (miR-663). To further evaluate miR-663 function, we overexpressed miR-663 in epithelial cells which resulted in cellular apoptosis. The bioinformatics analysis of the miR-663 target prediction, revealed a strong binding affinity to a 3' UTR region of Apoptosis Antagonizing Transcription Factor (AATF) mRNA. To demonstrate the binding of miR-663 to AATF mRNA, the putative miR-663 target site within the 3'-UTR region of AATF was cloned in luciferase vector and transfected to HEK293T cells. Luminescence data showed the downregulation of luciferase activity in cells that had the full length target region of the putative binding site, confirming that AATF is one of the targets for miR-663. This prompted us to further evaluate its role in a cancer cell line (MCF-7) to determine miR-663s' apoptotic function. The overexpression of miR-663 led to a significant increase in apoptosis of MCF-7 cells. Taken together, miR-663 may function as an 'apoptomiR' by inhibiting the anti-apoptotic gene AATF to induce apoptosis. These findings could have therapeutic implications for epithelial cell targeting in cancer therapy.

Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study.

In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.

"Picking winners": assessing new health technology.

Are evidence-based approaches ready for health technology?