ZFHX3 acts as a tumor suppressor in prostate cancer by targeting FTO-mediated m6A demethylation.

Zinc-finger homeobox 3 (ZFHX3, also known as ATBF1) suppresses prostatic tumorigenesis. ZFHX3 is frequently found to have numerous deletions in human prostate cancer (PCa). However, the underlying molecular function of ZFHX3 during prostatic tumorigenesis is not well understood. N6-methyladenosine (m6A) modification in RNA plays a critical role in the development of cancers; however, the relationship between ZFHX3 and m6A modification is largely unknown in PCa. In this study, we found that ZFHX3 knockdown decreased total m6A levels through enhancing the transcriptional activity of FTO in PCa cells. Importantly, FTO inhibition suppressed cell proliferation and rescued the promoting function of ZFHX3 knockdown on cell proliferation. In vivo, we verified that FTO was upregulated and ZFHX3 was decreased in PCa patients and that a high level of ZFHX3 is indispensable for low FTO expression and is correlated with better patient survival. Through transcriptome sequencing and MeRIP sequencing, we revealed that E2F2 and CDKN2C were the direct targets of FTO-mediated m6A modification and ZFXH3 was required for the regulation of FTO on E2F2 and CDKN2C expression. Unexpectedly, we uncovered that ZFHX3 expression was in return regulated by FTO in an m6A-dependent way. These findings establish a novel crosstalk mechanism between ZFHX3 and FTO in prostatic tumorigenesis.

Elucidating the cell metabolic heterogeneity during hematopoietic lineage differentiation based on Met-Flow.

Cell metabolism is critically involved in the differentiation of the hematopoietic lineage and, therefore, has attracted the attention of researchers, however, in-depth studies on cellular metabolic activity of hematopoietic cells (HCs) require attention. This investigation compared the metabolic activity of HCs at critical lineage differentiation stages, including hematopoietic stem cells (HSCs), hematopoietic progenitor cells (HPCs), and differentiated blood cells, via multiple methods and basic reference values. Primary metabolic processes of HCs, including anabolism, catabolism, phosphate, and glucose metabolism, were analyzed, and their maps were drawn. The data revealed that GLUT1 expression in HSCs was substantially higher than in all progenitor cells and mature myeloid blood cells, indicating their strong glucose uptake capacity. In myeloid differentiation, the ACAC expression of HPC2 was markedly higher than in neutrophils and monocytes. The ACAC, ASS1, ATP5A, and PRDX2 of HPC2 expression in lymphoid differentiation was substantially greater than in B and Natural-killer cells. CLP, CMP, GMP, MEP, and HPC1 inherit increased glucose uptake stem cell properties. In lymphocyte subsets, the expression of ACAC, ASS1, ATP5A, CPT1A, and PRDX2 in CD4+ T subgroups (naive and memory CD4+ T and nTreg) were elevated than in B subgroups (pro-, pre-, immature and mature Bs) and CD8+ T subgroups. Furthermore, leukemia stem cells (LSCs) had increased levels of ACAC, CPT1A, G6PD, IDH2, and PRDX2 than leukemia cells, indicating a stronger metabolic capacity of LSCs than differentiated leukemia cells.

Advances in the application of Raman spectroscopy in haematological tumours.

Hematologic malignancies are a diverse collection of cancers that affect the blood, bone marrow, and organs. They have a very unpredictable prognosis and recur after treatment. Leukemia, lymphoma, and myeloma are the most prevalent symptoms. Despite advancements in chemotherapy and supportive care, the incidence rate and mortality of patients with hematological malignancies remain high. Additionally, there are issues with the clinical diagnosis because several hematological malignancies lack defined, systematic diagnostic criteria. This work provided an overview of the fundamentals, benefits, and limitations of Raman spectroscopy and its use in hematological cancers. The alterations of trace substances can be recognized using Raman spectroscopy. High sensitivity, non-destructive, quick, real-time, and other attributes define it. Clinicians must promptly identify disorders and keep track of analytes in biological fluids. For instance, surface-enhanced Raman spectroscopy is employed in diagnosing gene mutations in myelodysplastic syndromes due to its high sensitivity and multiple detection benefits. Serum indicators for multiple myeloma have been routinely used for detection. The simultaneous observation of DNA strand modifications and the production of new molecular bonds by tip-enhanced Raman spectroscopy is of tremendous significance for diagnosing lymphoma and multiple myeloma with unidentified diagnostic criteria.