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Introduction: The pivotal roles of both abundant and rare bacteria in ecosystem function are widely acknowledged. Despite this, the diversity elevational patterns of these two bacterial taxa in different seasons and influencing factors remains underexplored, especially in the case of rare bacteria. Methods: Here, a metabarcoding approach was employed to investigate elevational patterns of these two bacterial communities in different seasons and tested the roles of soil physico-chemical properties in structuring these abundant and rare bacterial community. Results and discussion: Our findings revealed that variation in elevation and season exerted notably effects on the rare bacterial diversity. Despite the reactions of abundant and rare communities to the elevational gradient exhibited similarities during both summer and winter, distinct elevational patterns were observed in their respective diversity. Specifically, abundant bacterial diversity exhibited a roughly U-shaped pattern along the elevation gradient, while rare bacterial diversity increased with the elevational gradient. Soil moisture and N:P were the dominant factor leading to the pronounced divergence in elevational distributions in summer. Soil temperature and pH were the key factors in winter. The network analysis revealed the bacteria are better able to adapt to environmental fluctuations during the summer season. Additionally, compared to abundant bacteria, the taxonomy of rare bacteria displayed a higher degree of complexity. Our discovery contributes to advancing our comprehension of intricate dynamic diversity patterns in abundant and rare bacteria in the context of environmental gradients and seasonal fluctuations.
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BACKGROUND: Castration-resistant prostate cancer (CRPC) is a deadly malignancy without effective therapeutics. Cyclovirobuxine (CVB) can play an anticancer role by inhibiting mitochondrial function, regulating tumor cell apoptosis, dysregulating autophagy, and other mechanisms. This study aimed to examine the function and mechanism of CVB in CRPC to provide new insights into CRPC treatment. METHODS: The effect of CVB on PC3 and C4-2 cell viability was determined using a CCK8 assay. Core therapeutic targets of CVB in CRPC cells were identified using RNA sequencing, online database, and PPI network analyses. Western blotting, RT-qPCR and molecular docking were performed to evaluate the regulation of core targets by CVB. Utilizing GO and KEGG enrichment analyses, the probable anti-CRPC mechanism of CVB was investigated. Immunofluorescence, flow cytometry and colony formation assays were used to verify the potential phenotypic regulatory role of CVB in CRPC. RESULTS: CVB inhibited CRPC cell activity in a concentration-dependent manner. Mechanistically, it primarily regulated BRCA1-, POLD1-, BLM-, MSH2-, MSH6- and PCNA-mediated mismatch repair, homologous recombination repair, base excision repair, Fanconi anemia repair, and nucleotide excision repair pathways. Immunofluorescence, Western blot, flow cytometry and colony formation experiments showed that CVB induced DNA damage accumulation, cell apoptosis, and cell cycle arrest and inhibited CRPC cell proliferation. CONCLUSION: CVB can induce DNA damage accumulation in CRPC cells by targeting DNA repair pathways and then induce cell apoptosis and cell cycle arrest, eventually leading to inhibition of the long-term proliferation of CRPC cells.
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Enzalutamide (Enz) is a next-generation androgen receptor (AR) antagonist used to treat castration-resistant prostate cancer (CRPC). Unfortunately, the relapsing nature of CRPC results in the development of Enz resistance in many patients. Non-coding RNAs (ncRNAs) are RNA molecules that do not encode proteins, which include microRNAs (miRNA), long ncRNAs (lncRNAs), circular RNAs (circRNAs), and other ncRNAs with known and unknown functions. Recently, dysregulation of ncRNAs in CRPC, particularly their regulatory function in drug resistance, has attracted more and more attention. Herein, we introduce the roles of dysregulation of different ncRNAs subclasses in the development of CRPC progression and Enz resistance. Recently determined mechanisms of Enz resistance are discussed, focusing mainly on the role of AR-splice variant-7 (AR-V7), mutations, circRNAs and lncRNAs that act as miRNA sponges. Also, the contributions of epithelial-mesenchymal transition and glucose metabolism to Enz resistance are discussed. We summarize the different mechanisms of miRNAs, lncRNAs, and circRNAs in the progression of CRPC and Enz resistance, and highlight the prospect of future therapeutic strategies against Enz resistance.
