DNA and cell biology最新文献

Circular RNA (circRNA) is involved in the occurrence and development of various cancers. To this day, the expression and mechanism of circRNA in osteosarcoma (OS) remain unclear. We previously found that circ_0001060 was highly expressed in OS tumor tissues. In this work, we identified that high level expression of circ_0001060 was significantly associated with late clinical stage, larger tumor volume, higher frequency of metastasis, and poor prognosis in OS patients. Furthermore, we confirmed that silencing circ_0001060 inhibited the proliferation and migration of OS cell. Using bioinformatics analysis, we built three circRNA-miRNA-mRNA regulatory modules (circ_0001060-miR-203a-5p-TRIM21, circ_0001060-miR-208b-5p-MAP3K5, and circ_0001060-miR-203a-5p-PRKX), suggesting that these signaling axes may be involved in the inhibitory effect of circ_0001060 on OS. To sum up, circ_0001060 is a novel tumor biomarker for OS as well as a potential therapeutic target.

Circular RNAs (circRNAs) are a form of RNAs that lack coding potential. The role of such circRNAs in dental pulp stem cell (DPSC) osteo/odontogenic differentiation remains to be determined. In this study, circRNA expression profiles in DPSC osteo/odontogenic differentiation process were analyzed by RNA-seq. qRT-PCR was used to confirm the differential expression of circ_0005044, miR-296-3p, and FOSL1 in DPSC osteogenic differentiation process. Circ_0005044, miR-296-3p, and FOSL1 were knocked down or overexpressed. Osteoblastic activity and associated mineral activity were monitored via alkaline phosphatase (ALP) and alizarin red S (ARS) staining. Interactions between miR-296-3p, circ_0005044, and FOSL1 were assessed through luciferase reporter assays. Finally, an in vivo system was used to confirm the relevance of circ_0005044 to osteoblastic differentiation. As results, we detected significant circ_0005044 and FOSL1 upregulation in DPSC osteo/odontogenic differentiation process, as well as concomitant miR-296-3p downregulation. When knocking down circ_0005044 or overexpressed miR-296-3p, this significantly inhibited osteogenesis. Luciferase reporter assay confirmed that miR-296-3p was capable of binding to conserved sequences in the wild-type forms of both the circ_0005044 and FOSL1. Furthermore, knocking down circ_0005044 in vivo significantly attenuated bone formation. Therefore, the circ_0005044/miR-2964-3p/FOSL1 axis regulates DPSC osteo/odontogenic differentiation, which may provide potential molecular targets for dental-pulp complex regeneration.

Coronavirus 2 (COVID-19) has emerged as a new global pandemic, causing severe acute respiratory syndrome. Furthermore, the existence of antiphospholipid (APL) antibodies (Abs) and ultimately patient death may be linked to the occurrence of thrombotic events in patients with COVID-19. We aimed to investigate if there was a link between the presence of APL Abs and the severity of COVID-19 disease in patients at the Vali-Asr Hospital in Zanjan from June to July 2021. Real-time PCR was used to diagnose COVID-19 in 76 hospitalized patients. A total of 38 patients were hospitalized in the internal medicine ward and another 38 people were admitted to the intensive care unit of the Vali-Asr Educational Hospital in Iran's Zanjan region. Lupus anticoagulant (LAC) detection was done using the dilute Russell viper venom time method, and tests for anticardiolipin (ACL) Abs, IgG and IgM, and anti-beta2 glycoprotein 1 Abs, IgG and IgM, were done on blood and plasma samples of linked patients using the enzyme-linked immunosorbent assay technique. SPSS 24 was used to analyze data. Our findings showed that the presence of LAC was associated with disease severity in COVID-19 patients (p = 0.001). However, there was no significant relationship between APL Abs and mortality in patients affected with COVID-19. The evaluation of APL Abs, particularly LAC, in COVID-19 patients appears to be helpful in predicting the severity of the disease.

Cell adhesion and stable signaling regulation are fundamental ways of maintaining homeostasis. Among them, the Wnt/β-CATENIN signaling plays a key role in embryonic development and maintenance of body dynamic homeostasis. At the same time, the key signaling molecule β-CATENIN in the Wnt signaling can also function as a cytoskeletal linker protein to regulate tissue barriers, cell migration, and morphogenesis. Dysregulation of the balance between Wnt signaling and adherens junctions can lead to disease. How β-CATENIN maintains the independence of these two functions, or mediates the interaction and balance of these two functions, has been explored and debated for a long time. In this study, we will focus on five aspects of β-CATENIN chaperone molecules, phosphorylation of β-CATENIN and related proteins, epithelial mesenchymal transition, β-CATENIN homolog protein γ-CATENIN and disease, thus deepening the understanding of the Wnt/β-CATENIN signaling and the homeostasis between cell adhesion and further addressing related disease problems.

Caveolin-1 (CAV1) is one of the members of the caveolae, and the role of CAV1 in esophageal cancer (ESCA) is not completely clear. In this study, we found that expression of CAV1 was downregulated in ESCA in The Cancer Genome Atlas and the Genotype-Tissue Expression (GTEx) database and we also use immunohistochemistry of tissue microarray for verification. Then, we used bioinformatics methods to investigate the prognostic value of CAV1, influence on immune cell infiltration in tumor microenvironment (TME) and responding to immunotherapy in ESCA. Our result indicated that CAV1 designs an inflamed TME in ESCA based on the evidence that CAV1 positively correlated with immunomodulators, immune score, stomal score, cancer immunity cycles, tumor-infiltrating immune cells, T cell inflamed score, and immune checkpoints. Immunophenoscore, Tumor Immune Dysfunction and Exclusion algorithms, and the mutation analysis show that the downregulated CAV1 expression indicated higher tumor mutation burden and higher rate of response to immune checkpoint inhibitors (ICIs) in the low-expression group. In a word, our study demonstrated the impact of CAV1 to the TME in ESCA and it may be a new target for ESCA immunotherapy. In addition, the expression of CAV1 can predict the clinical response to ICIs, which may provide clinical treatment guidance.

Despite activated autophagy ameliorating hepatocyte steatosis and metabolic associated fatty liver disease (MAFLD), mechanisms underlying the beneficial roles of autophagy in hepatic deregulation of lipid metabolism remain undefined. We explored whether autophagy can ameliorate oleic acid (OA)-induced hepatic steatosis by suppressing pyroptosis. Pyroptosis is involved in hepatocyte steatosis induced by OA. In addition, autophagy flux was blocked in OA-treated hepatocytes. Treatment with OA induced lipid accumulation in liver cell line L-02, which was attenuated by rapamycin (Rap), an autophagy agonist, while aggravated by autophagy inhibitor bafilomycin A1 (Baf A1). Inversely, treatment with pyroptotic agonist Nigericin aggravated OA-induced hepatic steatosis, while pyroptosis antagonist disulfiram ameliorated this effect. Mechanistically, treatment with Rap downregulated the expression of pyroptosis-related proteins, including NLRP3, Caspase-1, IL-18, GSDMD expression evoked by OA, thus improving pyroptosis in hepatic steatosis. Significantly, overexpression of ATG5 obviously downregulated cleaved caspase-1 expressions without altering the total caspase1 expressions in hepatic cell steatosis. Taken together, our studies strongly demonstrated that the activation of ATG5 inhibits pyroptosis to improve hepatic steatosis and suggest autophagy activation as a potential therapeutic strategy for pyroptosis-mediated MAFLD.

Cancer stem cells (CSCs) drive tumor relapse, which is a major clinical challenge in colon cancer. Targeting CSCs presents a great opportunity in eradicating cancer cells and thus treatment of patients with cancer. However, the epigenetic control of the CSC signature and key molecules involved in colon cancer remains undefined. In this study, we demonstrated that alpha-1,3-glucosyltransferase (ALG8) is upregulated in colon cancer tissues compared with normal tissues. Overexpression of the ALG8 gene predicted poor overall survival and disease-free survival in colon cancer patients. Silencing of the ALG8 gene repressed the stemness of colon tumor cells. Xenograft mice transplanted with ALG8-deficient tumor cells significantly alleviated tumor burden and prolonged survival in comparison with control mice. Further analysis showed that ALG8 gene promoted cancer stemness through inducing glycosylation of LRP6, which activates the WNT/beta-catenin signaling pathway. Importantly, attenuation of the glycosylation using tunicamycin abrogated the effect of ALG8 gene on cancer stemness. Taken together, our findings demonstrated that ALG8 enhances colon tumorigenesis by activating the WNT/beta-catenin signaling pathway. Therefore, ALG8 gene is a potential therapeutic target in colon cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the United States. Although certain genetic predispositions may contribute to one's risk for developing CRC, dietary and lifestyle factors may play an important role as well. In a recent study in Nature, Dmitrieva-Posocco et al, reveal a potential protective role of the ketogenic diet in colorectal cancer growth and progression. Administration of a ketogenic diet to CRC-bearing mice demonstrated a tumor-suppressive effect. Specifically, the ketone body β-hydroxybutyrate (BHB) exhibited the ability to suppress epithelial cell proliferation and inhibit tumor growth. BHB acts on cancer cells through regulation of homeodomain-only protein Hopx, known regulator of CRC. Furthermore, BHB requires a surface receptor Hcar to induce Hopx expression and suppress proliferation of intestinal epithelial cells. Taken together, these results describe a new therapeutic approach of using dietary intervention for the prevention and treatment of colorectal cancer.

Oxidative stress leads to ovarian functional decline by inducing granulosa cell (GC) apoptosis. Circular RNA circFoxo3 acts as a critical factor in regulating cell cycle and apoptosis, and cellular senescence in tumor cells. However, function of circFoxo3 is little understood in oxidative stress-induced injury of follicular GCs. In this study, we aimed to illustrate the regulation pattern of circFoxo3 in GCs under oxidative stress. CircFoxo3 was confirmed to be expressed in both human and mouse GCs by amplification with divergent primers and sequencing. In vitro and in vivo ovarian oxidative stress model, the expression of circFoxo3, FOXO3 protein, and its downstream targets were examined by quantitative real-time PCR and Western blotting, respectively. Knockdown of circFoxo3 was performed to evaluate the effects of circFoxo3-mediated GC apoptosis in vitro. RNA pull-down was used to discover the protein that interacted with circFoxo3 so as to illustrate the mechanism of circFoxo3 in GCs. Our results demonstrated that circFoxo3 was significantly upregulated in hydrogen peroxide (H₂O₂)-treated GCs and a 3-nitropropionic acid (3-NP)-induced mouse model of ovarian oxidative stress. Protein level of transcriptional factor FOXO3 was also remarkably increased in both in vitro and in vivo oxidative stress model, but FOXO3 mRNA expression revealed no significant difference. Knockdown of endogenous circFoxo3 downregulated FOXO3 protein level and blocked H₂O₂-induced cell apoptosis. CircFoxo3 could pull down high levels of MDM2 protein that induced FOXO3 ubiquitination and degradation. Furthermore, knockdown of MDM2 and circFoxo3 showed remarkably higher level of apoptosis when compared with the knockdown of circFoxo3 alone. Our study suggested that circFoxo3 regulated FOXO3 protein level in GCs by reducing interactions between FOXO3 and MDM2. In conclusion, circFoxo3 was positively associated with FOXO3 protein and jointly played crucial roles in mediating GC apoptosis induced by oxidative stress.