SUMMARY Gut microbiota are linked to chronic inflammation and carcinogenesis. Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer patients. Here, we investigated the contribution of gut microbiota to chemoresistance in patients with colorectal cancer. We found that Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in patients with recurrence post chemotherapy, and was associated with patient clinicopathological characterisitcs. Furthermore, our bioinformatic and functional studies demonstrated that F. nucleatum promoted colorectal cancer resistance to chemotherapy. Mechanistically, F. nucleatum targeted TLR4 and MYD88 innate immune signaling and specific microRNAs to activate the autophagy pathway and alter colorectal cancer chemotherapeutic response. Thus, F. nucleatum orchestrates a molecular network of the Toll-like receptor, micro-RNAs, and autophagy to clinically, biologically, and mechanistically control colorectal cancer chemoresistance. Measuring and targeting F. nucleatum and its associated pathway will yield valuable insight into clinical management and may ameliorate colorectal cancer patient outcomes.

The 2019 novel coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected all aspects of human life. Rapid, accurate, sensitive and user friendly detection method is urgently needed to facilitate early intervention and control the spread of SARS-CoV-2. Here, we propose a one-pot visual SARS-CoV-2 detection system named “opvCRISPR” by integrating reverse transcription loop-mediated isothermal amplification (RT-LAMP) and Cas12a cleavage in a single reaction system. We demonstrate that the collateral activity against single-stranded DNA (ssDNA) reporters of activated Cas12a triggered by RT-LAMP amplicon increases detection sensitivity and makes detection results observable with naked eye. The opvCRISPR enables detection at nearly single molecule level in 45 min. We validate this method with 50 SARS-CoV-2 potentially infected clinical samples. The opvCRISPR diagnostic results provide 100% agreement with the Centers for Disease Control and Prevention (CDC)-approved quantitative RT-PCR assay. The opvCRISPR holds great potential for SARS-CoV-2 detection in next-generation point-of-care molecular diagnostics.

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BackgroundAccumulating evidence links colorectal cancer (CRC) with the intestinal microbiota. However, the disturbance of intestinal microbiota and the role of Fusobacterium nucleatum during the colorectal adenoma-carcinoma sequence have not yet been evaluated.Methods454 FLX pyrosequencing was used to evaluate the disturbance of intestinal microbiota during the adenoma-carcinoma sequence pathway of CRC. Intestinal microbiota and mucosa tumor-immune cytokines were detected in mice after introducing 1,2-dimethylhydrazine (DMH), F. nucleatum or Berberine (BBR), using pyrosequencing and Bio-Plex Pro™ cytokine assays, respectively. Protein expressions were detected by western blotting.ResultsThe levels of opportunistic pathogens, such as Fusobacterium, Streptococcus and Enterococcus spp. gradually increased during the colorectal adenoma-carcinoma sequence in human fecal and mucosal samples. F. nucleatum treatment significantly altered lumen microbial structures, with increased Tenericutes and Verrucomicrobia (opportunistic pathogens) (P < 0.05 = in wild-type C57BL/6 and mice with DMH treatment). BBR intervention reversed the F. nucleatum-mediated increase in opportunistic pathogens, and the secretion of IL-21/22/31, CD40L and the expression of p-STAT3, p-STAT5 and p-ERK1/2 in mice, compared with mice fed with F. nucleatum alone.ConclusionsF. nucleatum colonization in the intestine may prompt colorectal tumorigenesis. BBR could rescue F. nucleatum-induced colorectal tumorigenesis by modulating the tumor microenvironment and blocking the activation of tumorigenesis-related pathways.

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Background Globally, colorectal cancer (CRC) affects more than 1 million people each year. In addition to non-modifiable and other environmental risk factors, Fusobacterium nucleatum infection has been linked to CRC recently. In this study, we explored mechanisms underlying the role of Fusobacterium nucleatum infection in the progression of CRC in a mouse model. Methods C57BL/6 J-Adenomatous polyposis coli (APC) Min/J mice [APC (Min/+)] were treated with Fusobacterium nucleatum (109 cfu/mL, 0.2 mL/time/day, i.g., 12 weeks), saline, or FadA knockout (FadA−/−) Fusobacterium nucleatum. The number, size, and weight of CRC tumors were determined in isolated tumor masses. The human CRC cell lines HCT29 and HT116 were treated with lentiviral vectors overexpressing chk2 or silencing β-catenin. DNA damage was determined by Comet assay and γH2AX immunofluorescence assay and flow cytometry. The mRNA expression of chk2 was determined by RT-qPCR. Protein expression of FadA, E-cadherin, β-catenin, and chk2 were determined by Western blot analysis. Results Fusobacterium nucleatum treatment promoted DNA damage in CRC in APC (Min/+) mice. Fusobacterium nucleatum also increased the number of CRC cells that were in the S phase of the cell cycle. FadA−/− reduced tumor number, size, and burden in vivo. FadA−/− also reduced DNA damage, cell proliferation, expression of E-cadherin and chk2, and cells in the S phase. Chk2 overexpression elevated DNA damage and tumor growth in APC (Min/+) mice. Conclusions In conclusion, this study provided evidence that Fusobacterium nucleatum induced DNA damage and cell growth in CRC through FadA-dependent activation of the E-cadherin/β-catenin pathway, leading to up-regulation of chk2.

Non-small cell lung cancer (NSCLC) is a type of lung cancer which has a high mortality and low survival rate. Previous studies have revealed that long non-coding RNAs participate in tumorigenesis and metastasis in NSCLC. In the present study, the function of small nucleolar RNA host gene 12 (SNHG12) was investigated in NSCLC. Using reverse transcription-quantitative polymerase chain reaction analysis, it was identified that SNHG12 was significantly overexpressed in NSCLC specimens. Furthermore, overexpression of SNHG12 was identified to be associated with tumor progression and poor overall survival rates. Knockdown of SNHG12 in NSCLC cells could effectively induce cell apoptosis and suppress cell viability, proliferation, migration and invasion via inhibition of the epithelial-mesenchymal transition process. Furthermore, a direct interaction between microRNA (miR)-218 and the binding site of SNHG12 was identified. SNHG12 acted as an endogenous sponge for miR-218. Knockdown of SNHG12 upregulated the expression level of miR-218 as well as downregulating the Slug/zinc finger E-box-binding homeobox 2 EMT signaling pathway, and thus inhibited cell migration and invasion. Therefore, SNHG12 may serve as a key biomarker and a potential therapeutic target for the treatment of NSCLC.

Background: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide whose incidence has increased rapidly in recent years. There is growing evidence that the complex gut microbiota community plays an important role in the development of intestinal tumorigenesis. Summary: This review aimed to explore the correlation between gut microbiota and CRC as well as to identify the pathogens and their metabolites that affect CRC and the potential models of gut microbiota action. It promotes our understanding of the correlation between gut microbiota and CRC. Key Message: Our knowledge of the risk factors associated with gut microbiota for CRC development, as well as of the mechanism how intestinal bacteria act on colorectal tumorigenesis, has improved, leading to a better understanding of the correlation between gut microbiota and CRC. Practical Implications: The intestinal microbiota community has a close relationship with CRC by influencing the mechanism of the body and by regulating the physiological function of the colorectum and even the entire digestive system. Gut microbiota have been linked to CRC based upon their toxic and genotoxic metabolites production by fermentation of dietary ingredients. These metabolites could bind specific intestinal cell surface receptors and subsequently affect intracellular signal transduction. The mechanisms by which gut microbiota affect CRC development include the ‘Alpha-bug' model, the ‘driver-passenger' model and the ‘intestinal microbiota adaptions' model. This review promotes our understanding of the correlation between gut microbiota and CRC.