No abstract

In this study, for the first time, we demonstrated the presence of microRNAs and extracellular vesicles in human blastocoel fluid. The bioinformatic and comparative analyses identified the biological function of blastocoel fluid microRNAs and suggested a potential role inside the human blastocyst. We found 89 microRNAs, expressed at different levels, able to regulate critical signaling pathways controlling embryo development, such as pluripotency, cell reprogramming, epigenetic modifications, intercellular communication, cell adhesion and cell fate. Blastocoel fluid microRNAs reflect the miRNome of embryonic cells and their presence, associated with the discovery of extracellular vesicles, inside blastocoel fluid, strongly suggests their important role in mediating cell communication among blastocyst cells. Their characterization is important to better understand the earliest stages of embryogenesis and the complex circuits regulating pluripotency. Moreover, blastocoel fluid microRNA profiles could be influenced by blastocyst quality, therefore, microRNAs might be used to assess embryo potential in IVF cycles.

MiR-671-5p is encoded by a gene localized at 7q36.1, a region amplified in human glioblastoma multiforme (GBM), the most malignant brain cancer. To investigate whether expression of miR-671-5p were altered in GBM, we analyzed biopsies from a cohort of forty-five GBM patients and from five GBM cell lines. Our data show significant overexpression of miR-671-5p in both biopsies and cell lines. By exploiting specific miRNA mimics and inhibitors, we demonstrated that miR-671-5p overexpression significantly increases migration and to a less extent proliferation rates of GBM cells. Through a combined in silico and in vitro approach, we identified CDR1-AS, CDR1, VSNL1 as downstream miR-671-5p targets in GBM. Expression of these genes significantly decreased both in GBM biopsies and cell lines and negatively correlated with that of miR-671-5p. Based on our data, we propose that the axis miR-671-5p / CDR1-AS / CDR1 / VSNL1 is functionally altered in GBM cells and is involved in the modification of their biopathological profile.

Relationships between residual feed intake (RFI) and other performance variables were determined using 54 purebred Angus steers. Individual feed intake and BW gain were recorded during a 70-d post-weaning period to calculate RFI. After the 70-d post-weaning test, steers were fed a finishing ration to a similar fat thickness (FT), transported to a commercial facility, and slaughtered. A subsample of carcasses (n = 32) was selected to examine the relationships among RFI, meat quality, and palatability. Steers were categorized into high (> 0.5 SD above the mean; n = 16), medium (mid; +/- 0.5 SD from the mean; n = 21), and low (< 0.5 SD below the mean; n = 17) RFI groups. No differences were detected in ADG, initial BW, and d 71 BW among the high, mid, and low RFI steers. Steers from the high RFI group had a greater DMI (P = 0.004) and feed conversion ratio (FCR; DMI:ADG; P = 0.002) compared with the low RFI steers. Residual feed intake was positively correlated with DMI (r = 0.54; P = 0.003) and FCR (r = 0.42; P = 0.002), but not with initial BW, d 71 BW, d 71 ultrasound FT, initial ultrasound LM area, d 71 ultrasound LM area, or ADG. The FCR was positively correlated with initial BW (r = 0.46; P = 0.0005), d 71 BW (r = 0.34; P = 0.01), and DMI (r = 0.40; P = 0.003) and was negatively correlated with ADG (r = -0.65; P = 0.001). There were no differences among RFI groups for HCW, LM area, FT, KPH, USDA yield grade, marbling score, or quality grade. Reflectance color b* scores of steaks from high RFI steers were greater (P = 0.02) than those from low RFI steers. There was no difference between high and low RFI groups for LM calpastatin activity. Warner-Bratzler shear force and sensory panel tenderness and flavor scores of steaks were similar across RFI groups. Steaks from high RFI steers had lower (P = 0.04) off-flavor scores than those from low RFI steers. Cook loss percentages were greater (P = 0.005) for steaks from low RFI steers than for those from mid RFI steers. These data support current views that RFI is independent of ADG, but is correlated with DMI and FCR. Importantly, the data also support the hypothesis that there is no relationship between RFI and beef quality in purebred Angus steers.

For two decades Vogelstein's model has been the paradigm for describing the sequence of molecular changes within protein-coding genes that would lead to overt colorectal cancer (CRC). This model is now too simplistic in the light of recent studies, which have shown that our genome is pervasively transcribed in RNAs other than mRNAs, denominated non-coding RNAs (ncRNAs). The discovery that mutations in genes encoding these RNAs [i.e., microRNAs (miRNAs), long non-coding RNAs, and circular RNAs] are causally involved in cancer phenotypes has profoundly modified our vision of tumour molecular genetics and pathobiology. By exploiting a wide range of different mechanisms, ncRNAs control fundamental cellular processes, such as proliferation, differentiation, migration, angiogenesis and apoptosis: these data have also confirmed their role as oncogenes or tumor suppressors in cancer development and progression. The existence of a sophisticated RNA-based regulatory system, which dictates the correct functioning of protein-coding networks, has relevant biological and biomedical consequences. Different miRNAs involved in neoplastic and degenerative diseases exhibit potential predictive and prognostic properties. Furthermore, the key roles of ncRNAs make them very attractive targets for innovative therapeutic approaches. Several recent reports have shown that ncRNAs can be secreted by cells into the extracellular environment (i.e., blood and other body fluids): this suggests the existence of extracellular signalling mechanisms, which may be exploited by cells in physiology and pathology. In this review, we will summarize the most relevant issues on the involvement of cellular and extracellular ncRNAs in disease. We will then specifically describe their involvement in CRC pathobiology and their translational applications to CRC diagnosis, prognosis and therapy.