CircRNAs are a class of noncoding RNA species with a circular configuration that is formed by either typical spliceosome-mediated or lariat-type splicing. The expression of circRNAs is usually abnormal in many cancers. Several circRNAs have been demonstrated to play important roles in carcinogenesis. In this review, we will first provide an introduction of circRNAs biogenesis, especially the regulation of circRNA by RNA-binding proteins, then we will focus on the recent findings of circRNA molecular mechanisms and functions in cancer development. Finally, some open questions are also discussed.
Alzheimer's disease (AD) is the most common cause of dementia and cannot be cured. The etiology and pathogenesis of AD is still not fully understood, the genetics is considered to be one of the most important factors for AD onset, and the identified susceptible genes could provide clues to the AD mechanism and also be the potential targets. MicroRNA-146a-5p (miR-146a) is well known in the regulation of the inflammatory response, and the functional SNP of miR-146a was associated with AD risk. In this study, using a noninvasive nasal administration, we discovered that a miR-146a agomir (M146AG) rescued cognitive impairment in the APP/PS1 transgenic mouse and alleviated the overall pathological process in the AD mouse model, including neuroinflammation, glia activation, Ab deposit, and tau phosphorylation in hippocampi. Furthermore, the transcriptional analysis revealed that besides the effect of neuroinflammation, M146AG may serve as a multi-potency target for intervention in AD. In addition, Srsf6 was identified as a target of miR-146a, which may play a role in AD progression. In conclusion, our study supports that the nasal-to-brain pathway is efficient and operable for the brain administration of microRNAs (miRNAs), and that miR-146a may be a new potential target for AD treatment.
The gummosis disease is caused by Botryosphaeria dothidea (Moug. ex. Fr) Ces. et de Not., and it is one of the most important diseases of stone fruits worldwide. The use of biocontrol as an alternative approach to synthetic chemical fungicides has aroused general concern about how to control plant diseases that are caused by phytopathogens. The aim of this study is to isolate Bacillus strains from raw honeys with the capacity to inhibit B. dothidea and to explore the mechanisms by which they could be used in the biocontrol of peach gummosis. Bacillus amyloliquefaciens SYBC H47 was isolated and identified on the basis of its physiological and biochemical characteristics and its 16S rRNA and gyrB gene sequences. The cell suspension and the cell-free supernatant of its culture showed significant antifungal activity against Aspergillus niger, Mucor racemosus, Fusarium oxysporum, Penicillium citrinum, and Candida albicans by agar-diffusion assays. The primary antifungal substances were bacillomycin L, fengycin, and surfactin, which were analyzed by HPLC LC/ESI-MS/MS. Bacillomycin L showed the best inhibitory effect against conidial germination of B. dothidea, followed by fengycin and surfactin. Surfactin had limited effects on mycelial growth, contrary to those of bacillomycin L and fengycin. However, a mixture of the three lipopeptides had a synergistic effect that disrupted the structure of the conidia and mycelia. In order to reduce the production cost, the use of waste frying peanut oil and soy oil as the sole carbon source increased the lipopeptide yield levels by approximately 17% (2.42 g/L) and 110% (4.35 g/L), respectively. In a field trial, the decreases in the infected gummosis rate (IGR) and the disease severity index (DSI) through cell suspension treatments were 20% and 57.5% (in 2014), respectively, and 40% and 57.5% (in 2015), respectively, in comparison with the control. In conclusion, B. amyloliquefaciens SYBC H47 could inhibit the germination of conidia and the growth of mycelia from B. dothidea; therefore, this strain behaves as a potential biocontrol agent against the gummosis disease.
MicroRNA-146a (miR-146a) acts as a pivotal regulatory molecule in immune response and various diseases, such as carcinoma and autoimmune diseases. Growing evidences have demonstrated the association of miR-146a gene single-nucleotide polymorphisms (SNPs) with risk of several diseases, but no genetic relevance studies of miR-146a gene polymorphisms to sepsis have been reported by now. Our study has analyzed the association of sepsis with two functional miR-146a gene SNPs rs2910164 G/C and rs57095329 A/G in a Chinese Han population (226 sepsis cases; 206 healthy controls). Our results indicated a higher prevalence of the miR-146a gene SNP rs2910164 C allele and CC genotype in patients with severe sepsis (rs2910164G versus rs2910164C: P = 0.0029, odds ratio (OR) = 1.664; GG+GC versus CC: P = 0.0045, OR = 1.947). Neither the genotype nor the allele in rs57095329 showed significant differences between the septic cases and the controls (P = 0.5901 and 0.3580, resp.), and no significant difference was observed in the subgroups. In addition, we confirmed that the two SNPs rs2910164 and rs57095329 could functionally affect the miR-146a expression levels and the reduction of miR146a was accompanied with the upregulation of the expression levels of TRAF-6 and IRAK-1 in severe sepsis patients. This present study might provide valuable clinical evidence that miR-146a gene polymorphism rs2910164 is associated with the risk of severe sepsis.
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