Ovarian cancer is the eighth most common cancer in women worldwide, and epithelial ovarian cancer (EOC) represents 90% of cases. Nerve growth factor (NGF) and its high affinity receptor tyrosine kinase A receptor (TRKA) have been associated with the development of several types of cancer, including EOC; both NGF and TRKA levels are elevated in this pathology. EOC presents high angiogenesis and several molecules have been reported to induce this process. NGF increases angiogenesis through its TRKA receptor on endothelial cells, and by indirectly inducing vascular endothelial growth factor expression. Other molecules controlled by NGF include ciclooxigenase-2, disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) and calreticulin (CRT), proteins involved in crucial processes needed for EOC progression. These molecules could be modified through microRNA regulation, which could be regulated by NGF. MicroRNAs are the widest family of non-coding RNAs; they bind to 3′-UTR of mRNAs to inhibit their translation, to deadenilate or to degraded them. In EOC, a deregulation in microRNA expression has been described, including alterations of miR-200 family, cluster-17-92, and miR-23b, among others. Since the NGF-microRNA relationship in pathologies has not been studied, this review proposes that some microRNAs could be associated with NGF/TRKA activation, modifying protein levels needed for EOC progression.

Chile is one of the largest consumers of sugar-sweetened beverages (SSB) world-wide. However, it is unknown whether the effects from this highly industrialized food will mimic those reported in industrialized countries or whether they will be modified by local lifestyle or population genetics. Our goal is to evaluate the interaction effect between SSB intake and T2D susceptibility on fasting glucose. We calculated a weighted genetic risk score (GRSw) based on 16 T2D risk SNPs in 2828 non-diabetic participants of the MAUCO cohort. SSB intake was categorized in four levels using a food frequency questionnaire. Log-fasting glucose was regressed on SSB and GRSw tertiles while accounting for socio-demography, lifestyle, obesity, and Amerindian ancestry. Fasting glucose increased systematically per unit of GRSw (β = 0.02 ± 0.006, p = 0.00002) and by SSB intake (β[cat4] = 0.04 ± 0.01, p = 0.0001), showing a significant interaction, where the strongest effect was observed in the highest GRSw-tertile and in the highest SSB consumption category (β = 0.05 ± 0.02, p = 0.02). SNP-wise, SSB interacted with additive effects of rs7903146 (TCF7L2) (β = 0.05 ± 0.01, p = 0.002) and with the G/G genotype of rs10830963 (MTNRB1B) (β = 0.19 ± 0.05, p = 0.001). Conclusions: The association between SSB intake and fasting glucose in the Chilean population without diabetes is modified by T2D genetic susceptibility.

Epithelial ovarian cancer (EOC) is a disease that causes 140,000 deaths every year. Nerve growth factor (NGF) and its high affinity receptor TRKA play important roles in follicular maturation, follicle-stimulating hormone (FSH) receptor acquisition and ovulation in normal ovary. Also, NGF has many roles in EOC cells: increasing survival, proliferation, cyclooxigenase-2 (COX-2), vascular endothelial growth factor (VEGF) and metalloproteinase ADAM17 expression. Besides, NGF inhibits calreticulin translocation from the endoplasmic reticulum to cell surface, possibly diminishing the efficacy of immunogenic therapies in EOC. Additionally, NGF acts as an angiogenic factor by a direct stimulation of migration, differentiation and proliferation of endothelial cells. Among the numerous factors actually described to be important in many types of cancer, including EOC, are the microRNAs (miRs). Indeed, it has been found that miR-143 is downregulate in EOC, which correlates with an increase of COX-2; concomitantly, NGF increases COX-2 as mentioned. Furthermore, NGF increases miR-222 and its target is the metalloproteinase inhibitor TIMP3, increasing the ADAM17 function. Also, NGF increases cMYC transcription factor in EOC, which decreases miR-23 levels regulating proteins involved in cell cycle and tumor growth. Therefore, NGF/TRKA signaling pathways alter the expression of many proteins and deregulate miRs in EOC, leading to the progression of this cancer.