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MicroRNAs (miRNAs) have been shown to be dysregulated in virus-related cancers; however, miRNA regulation of virus-related cancer development and progression remains poorly understood. Here, we report that miR-148a is repressed by hepatitis B virus (HBV) X protein (HBx) to promote cancer growth and metastasis in a mouse model of hepatocellular carcinoma (HCC). Hematopoietic pre-B cell leukemia transcription factor-interacting protein (HPIP) is an important regulator of cancer cell growth. We used miRNA target prediction programs to identify miR-148a as a regulator of HPIP. Expression of miR-148a in hepatoma cells reduced HPIP expression, leading to repression of AKT and ERK and subsequent inhibition of mTOR through the AKT/ERK/FOXO4/ATF5 pathway. HBx has been shown to play a critical role in the molecular pathogenesis of HBV-related HCC. We found that HBx suppressed p53-mediated activation of miR-148a. Moreover, expression of miR-148a was downregulated in patients with HBV-related liver cancer and negatively correlated with HPIP, which was upregulated in patients with liver cancer. In cultured cells and a mouse xenograft model, miR-148a reduced the growth, epithelial-to-mesenchymal transition, invasion, and metastasis of HBx-expressing hepatocarcinoma cells through inhibition of HPIP-mediated mTOR signaling. Thus, miR-148a activation or HPIP inhibition may be a useful strategy for cancer treatment., Introduction MicroRNAs (miRNAs) are small noncoding RNA molecules that inhibit gene expression by interacting preferentially with the 3'-untranslated regions (3'-UTRs) of target mRNAs (1), (2). These interactions may cause either [...]

Biofilm formation is a survival strategy by which microorganisms adapt to environmental challenges. It is regulated by various signals, such as the second messenger c-di-GMP. We previously found that the Flm chemosensory pathway could respond to chemical signals and regulate biofilm formation. This regulation is independent of c-di-GMP. A previous study revealed that the response regulator FlmD is involved in biofilm formation; however, how chemical signals are transmitted downstream of FlmD remained unclear. In the present study, transcriptome analysis and gel shift assay reveal that SoxR, a transcriptional activator of the efflux transporter acrAB-tolC operon, mediates the downstream signaling of FlmD. Phosphorylated FlmD interacts with SoxR and disrupts the interaction between SoxR and the acrAB-tolC operon. It causes a decrease in the expression of acrAB-tolC operon. The downregulation of acrA, acrB, or tolC gene expression results in making less biofilm formation. In conclusion, we identified that the transcription regulator SoxR plays a role in the c-di-GMP independent regulation of biofilm formation in Comamonas testosteroni. [ABSTRACT FROM AUTHOR]

Background: Gut-brain axis might play an important role in cognitive impairments by various diseases including Alzheimer's disease (AD)., Objective: To investigate the differences in gut microbial composition, intestinal barrier function, and systemic inflammation in patients with AD or mild cognitive impairment (MCI), and normal control (NC) cases., Methods: A total of 118 subjects (45 AD, 38 MCI, and 35 NC) were recruited. Cognitive function was assessed using Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment Scale (MoCA). Functional ability was assessed using Activity of Daily Living Scale (ADL). The composition of gut microbiome was examined by 16S rRNA high-throughput sequencing. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict functional transfer of gut microbiota. Gut barrier dysfunction was evaluated by measuring the levels of diamine oxidase (DAO), D-lactic acid (DA), and endotoxin (ET). The serum high-sensitivity C-reactive protein (hs-CRP) level was used to indicate systemic inflammation., Results: Compared with normal controls, patients with cognitive impairments (AD and MCI) had lower abundance of Dorea and higher levels of DAO, DA, and ET. Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that the pathways related to glycan biosynthesis and metabolism increased in MCI patients, while the ones related to membrane transport decreased. The abundance of Bacteroides and Faecalibacterium was negatively correlated with the content of ET, and positively correlated with the scores of MMSE and MoCA. The hs-CRP levels were similar among the three groups. A significant negative correlation was observed between the severity of gut barrier dysfunction and cognitive function., Conclusion: Cognitive impairments might be associated with gut microbial dysbiosis and intestinal barrier dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pei, Lu, Li, Jiang and Wang.)

Nonhuman primates (NHPs) such as monkeys are the closest living relatives to humans and are the best available models for causative studies of human health and diseases. Gut microbiomes are intensively involved in host health. In this study, by large-scale cultivation of microbes from fecal samples of monkeys, we obtained previously uncultured bacterial species and constructed a Macaca fascicularis Gut Microbial Biobank (MfGMB). The MfGMB consisted of 250 strains that represent 97 species of 63 genera, 25 families, and 4 phyla. The information of the 250 strains and the genomes of 97 cultured species are publicly accessible. The MfGMB represented nearly 50% of core gut microbial compositions at the genus level and covered over 80% of the KO-based known gut microbiome functions of M. fascicularis . Data mining showed that the bacterial species in the MfGMB were prevalent not only in NHPs gut microbiomes but also in human gut microbiomes. This study will help the understanding and future investigations on how gut microbiomes interact with their mammalian hosts., Competing Interests: The authors declare no conflict of interests., (© 2022 The Authors. mLife published by John Wiley & Sons Australia, Ltd. on behalf of Institute of Microbiology, Chinese Academy of Sciences.)