Hernandez, E. | Search bioRxiv

bioRxiv2018

IFN-γ induces epithelial-to-mesenchymal transition of cancer cells via an unique microRNA processing

Interferon-{gamma} (IFN{gamma}) is a potent cytokine in modulating tumor immunity and tumoricidal effects. We demonstrate a new function of IFN{gamma} in inducing epithelial-to-mesenchymal transition (EMT) in normal and cancer cells from different cell types. IFN{gamma} activates JAK-STAT signaling pathway leading to the transcription of IFN-stimulated genes (ISGs), such as interferon-induced tetratricopeptide repeat 5 (IFIT5). We unveil a new function of IFIT5 complex in degrading precursor microRNAs (pre-miRNA) that include pre-miR-363 from the miR-106a-363 cluster, as well as pre-miR-101 and pre-miR-128 with a similar 5-end structure with pre-miR-363. Noticeably, these suppressive miRNAs have similar functions by targeting EMT transcription factors in prostate cancer (PCa) cells. We further demonstrated that IFIT5 plays a critical role in IFN{gamma}-induced cell invasiveness in vitro and lung metastasis in vivo. Clinically, IFIT5 is highly elevated in high-grade PCa and its expression inversely correlates with these suppressive miRNAs. Altogether, this study unveils pro-tumorigenic role of the IFN pathway via a new mechanism of action, which certainly raises concern about its clinical application.

cancer biology↗

bioRxiv2018

Environmental and Socioeconomic Factors Associated with West Nile Virus

Environmental and socioeconomic risk factors associated with West Nile Virus cases were investigated in the Northern San Joaquin Valley region of California, a largely rural area. The study included human West Nile Virus (WNV) cases from the years 2011-2015 in the three county area of San Joaquin, Stanislaus and Merced Counties, and examined whether factors were associated with WNV using census tracts as the unit of analysis. Environmental factors included temperature, precipitation, mosquitoes positive for WNV, and habitat. Socioeconomic variables included age, education, housing age, home vacancies, median income, population density, ethnicity, and language spoken. Chi-squared independence tests were used to examine whether each variable was associated with WNV in each county, and then also used for the three counties combined. Logistic regression was used for a three-county combined analysis, to examine which environmental and socioeconomic variables were most likely associated with WNV cases. The chi-squared tests found that the variables associated with WNV varied in each of the three counties. The chi-squared tests for data combined from the three counties found that WNV cases were significantly associated with mosquitoes positive for WNV, urban habitat, higher home vacancies, higher population density, higher education, and ethnicity. Logistic regression analysis revealed that overall, the environmental factors precipitation, mean temperature, and WNV positive mosquitoes were the strongest predictors of WNV cases. Results support efforts of mosquito control districts, which aim for source reduction of mosquito breeding sites. In addition, findings suggest that residents with higher income and education may be more aware of WNV and its symptoms, and more likely to request testing from physicians. Lower income and education residents may not be aware of WNV. Public health education might increase its prevention messages about vector-borne disease in the various languages of the region, which would contribute overall to public health in the region.

epidemiology↗