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Simple Summary: Epigenetic modification plays an important regulatory role in breast cancer progression. However, the relationship between epigenetic modification with tumor metabolism has not yet been fully elucidated. PDK1, as a key enzyme in glucose metabolism, mediates multiple tumors development. But, the mechanism of epigenetic modification in regulating PDK1 remains unclear in breast cancer. Here, we demonstrated that HDAC2 and EZH2 upregulated PDK1 expression through inhibiting miR-148a. Importantly, miR-148a targeting PDK1 regulated breast cancer cells glycolysis, invasion, epithelial-mesenchymal transition (EMT) and Adriamycin resistance. Our results suggested that the HDAC2/EZH2/miR-148a/PDK1 axis may be a promising potential therapeutic strategy. Background: Breast cancer has one of highest morbidity and mortality rates for women. Abnormalities regarding epigenetics modification and pyruvate dehydrogenase kinase 1 (PDK1)-induced unusual metabolism contribute to breast cancer progression and chemotherapy resistance. However, the role and mechanism of epigenetic change in regulating PDK1 in breast cancer remains to be elucidated. Methods: Gene set enrichment analysis (GSEA) and Pearson's correlation analysis were performed to analyze the relationship between histone deacetylase 2 (HDAC2), enhancer of zeste homologue 2 (EZH2), and PDK1 in database and human breast cancer tissues. Dual luciferase reporters were used to test the regulation between PDK1 and miR-148a. HDAC2 and EZH2 were found to regulate miR-148a expression through Western blotting assays, qRT-PCR and co-immunoprecipitation assays. The effects of PDK1 and miR-148a in breast cancer were investigated by immunofluorescence (IF) assay, Transwell assay and flow cytometry assay. The roles of miR-148a/PDK1 in tumor growth were investigated in vivo. Results: We found that PDK1 expression was upregulated by epigenetic alterations mediated by HDAC2 and EZH2. At the post-transcriptional level, PDK1 was a new direct target of miR-148a and was upregulated in breast cancer cells due to miR-148a suppression. PDK1 overexpression partly reversed the biological function of miR-148a—including miR-148a's ability to increase cell sensitivity to Adriamycin (ADR) treatment—inhibiting cell glycolysis, invasion and epithelial–mesenchymal transition (EMT), and inducing apoptosis and repressing tumor growth. Furthermore, we identified a novel mechanism: DNMT1 directly bound to EZH2 and recruited EZH2 and HDAC2 complexes to the promoter region of miR-148a, leading to miR-148a downregulation. In breast cancer tissues, HDAC2 and EZH2 protein expression levels also were inversely correlated with levels of miR-148a expression. Conclusion: Our study found a new regulatory mechanism in which EZH2 and HDAC2 mediate PDK1 upregulation by silencing miR-148a expression to regulate cancer development and Adriamycin resistance. These new findings suggest that the HDAC2/EZH2/miR-148a/PDK1 axis is a novel mechanism for regulating cancer development and is a potentially promising target for therapeutic options in the future. [ABSTRACT FROM AUTHOR]

Irrigation, fertilization, and variety are important factors affecting potato production in northwest China. Field experiments (2021 and 2022) were performed to investigate the effects of irrigation and fertilization on the plant growth and soil microbial population of different potato varieties. Three irrigation levels were used, i.e., 100% ETc (W1), 80% ETc (W2), and 60% ETc (W3), with ETc standing for crop evapotranspiration. Three fertilization levels were used (N-P-K), i.e., 240-120-300 kg ha−1 (F1), 180-90-225 kg ha−1 (F2), and 120-60-150 kg ha−1 (F3). Three variety types were used, i.e., Feiurita (V1), Longshu 7 (V2), and Qingshu 9 (V3). These factors significantly influenced tuber yield (TY), net income (NI), and water productivity (WP). TY, NI, WP, total nitrogen accumulation (TNA), and nitrogen use efficiency (NUE) peaked at F2. Fertilization significantly impacted soil bacteria quantity (SBQ), fungi quantity (SFQ), and actinomycetes quantity (SAQ). TY, NI, SBQ, SFQ, and SAQ were highest at W2. Soil microbial population was strongly correlated with TY, NI, WP, TNA, and NUE. Comprehensively, this study suggests that irrigation that is varied from 248 to 266 mm, and fertilization (N-P-K) that is varied from 149.09-74.55-186.36 to 212.73-106.36-265.91 kg ha−1 can promote the potato industry's sustainable development and provide important references for the optimal field management of potato cultivation in northwest China. [ABSTRACT FROM AUTHOR]