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Epidemiological studies indicate that obesity negatively affects the progression and treatment of cervical-uterine cancer. Recent evidence shows that a subpopulation of adipose-derived stem cells can alter cancer properties. In the present project, we described for the first time the impact of adipose-derived stem cells over the malignant behavior of cervical cancer cells. The transcriptome of cancer cells cultured in the presence of stem cells was analyzed using RNA-seq. Changes in gene expression were validated using digital-PCR. Bioinformatics tools were used to identify the main transduction pathways disrupted in cancer cells due to the presence of stem cells. In vitro and in vivo assays were conducted to validate cellular and molecular processes altered in cervical cancer cells owing to stem cells. Our results show that the expression of 95 RNAs was altered in cancer cells as a result of adipose-derived stem cells. Experimental assays indicate that stem cells provoke an increment in migration, invasion, angiogenesis, and tumorigenesis of cancer cells; however, no alterations were found in proliferation. Bioinformatics and experimental analyses demonstrated that the NF-kappa B signaling pathway is enriched in cancer cells due to the influence of adipose-derived stem cells. Interestingly, the tumor cells shift their epithelial to a mesenchymal morphology, which was reflected by the increased expression of specific mesenchymal markers. In addition, stem cells also promote a stemness phenotype in the cervical cancer cells. In conclusion, our results suggest that adipose-derived stem cells induce cervical cancer cells to acquire malignant features where NF-kappa B plays a key role.

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Stress granules are cytoplasmic foci that directly respond to the protein synthesis status of the cell. Various environmental insults, such as oxidative stress or extreme heat, block protein synthesis; consequently, mRNA will stall in translation, and stress granules will immediately form and become enriched with mRNAs. P54 DEAD box RNA helicases are components of RNA granules such as P-bodies and stress granules. We studied the expression, in cytoplasmic foci, of both zebrafish P54 RNA helicases (P54a and P54b) during development and found that they are expressed in cytoplasmic granules under both normal conditions and stress conditions. In zebrafish embryos exposed to heat shock, some proportion of P54a and P54b helicases move to larger granules that exhibit the properties of genuine stress granules. Knockdown of P54a and/or P54b in zebrafish embryos produces developmental abnormalities restricted to the posterior trunk; further, these embryos do not form stress granules, and their survival upon exposure to heat-shock conditions is compromised. Our observations fit the model that cells lacking stress granules have no resilience or ability to recover once the stress has ended, indicating that stress granules play an essential role in the way organisms adapt to a changing environment.

Background: Scarb2 or Limp2 belong to a subfamily of Scavenger receptors described as lysosomal transmembrane glycosylated receptors, that are mutated in the human syndrome AMRF (action myoclonus-renal failure). The zebrafish insertional mutant scarb2a hi1463Tg has notochord defects, the notochord is a defining feature of chordates running along the center of the longitudinal axis and it is essential for forming the spinal column in all vertebrates. Results: There are three paralogous scarb2 genes in zebrafish; scarb2a, scarb2b, and scarb2c. Both Scarb2a and Scarb2b proteins lack the classical di-leucine motif. We found that scarb2a hi1463Tg homozygous zebrafish embryos have a null mutation impairing vacuole formation in the notochord and simultaneously disrupting proper formation of the basement membrane resulting in its thickening at the ventral side of the notochord, which may be the cause for the anomalous upward bending observed in the trunk. Through whole-mount in situ hybridization, we detected scarb2a mRNA expression in the notochord and in the brain early in development. However, it is puzzling that scarb2a notochord mRNA expression is short-lived in the presumptive notochord and precedes the complete differentiation of the notochord. Conclusions: This work describes a novel function for the Scarb2 receptor as an essential glycoprotein for notochord development. Developmental Dynamics 245:508-519,

Chromatin regulation and organization are essential processes that regulate gene activity. The CCCTC-binding factor (CTCF) is a protein with different and important molecular functions related with chromatin dynamics. It is conserved since invertebrates to vertebrates, posing it as a factor with an important role in the physiology. In this work, we aimed to understand the distribution and functional relevance of CTCF during the embryonic development of the zebrafish (Danio rerio). We generated a zebrafish specific anti-Ctcf antibody, and found this protein to be ubiquitous, through different stages and tissues. We used the CRISPR-Cas9 system to induce molecular alterations in the locus. This resulted in early lethality. We delayed the lethality performing knockdown morpholino experiments, and found an aberrant embryo morphology involving malformations in structures through all the length of the embryo. These phenotypes were rescued with human CTCF mRNA injections, showing the specificity of the morpholinos and a partial functional conservation between the fish and the human proteins. Lastly, we found that the pro-apoptotic genes p53 and bbc3/PUMA are deregulated in the ctcf morpholino-injected embryos. In conclusion, CTCF is a ubiquitous factor during the zebrafish development, which regulates the correct formation of different structures of the embryo, and its deregulation impacts on essential cell survival genes. Overall, this work provides a basis to look for the particular functions of CTCF in the different developing tissues and organs of the zebrafish.

This is the first study showing the significant association between the BDNF rs6265 AA (Met/Met) genotype and overweight/obesity in Mexican pediatric population.