Background: Bladder cancer (BLCA) is a common and deadly disease that results in a reduced quality of life for the patients and a significant economic burden on society. A better understanding of tumorigenesis is needed to improve clinical outcomes. Recent evidence places the RNA modification m1A and its regulatory proteins TRMT6/TRMT61A and ALKBH3 in BLCA pathogenesis.
Methods: TRMT6/TRMT61A, ALKBH1, and ALKBH3 expression was examined in human BLCA cell lines and a normal urinary tract epithelium cell line through qRT-PCR and western blot analysis. Prestoblue Cell Viability Reagent, wound-healing assay, and live-cell imaging-based cell displacement analysis, were conducted to assess proliferation, migration, and displacement of this BLCA cell line panel. Cell survival was assessed after inducing cellular stress and activating the unfolded protein response (UPR) with tunicamycin. Moreover, siRNA-mediated gene silencing in two BLCA cell lines (5637 and HT1197) was conducted to investigate the biological roles of TRMT6/TRMT61A.
Results: Heterogeneous morphology, proliferation, displacement, tunicamycin sensitivity, and expression levels of m1A regulators were observed among the panel of cell lines examined. In general, TRMT61A expression was increased in BLCA cell lines when compared to SV-HUC-1. Depletion of TRMT6/TRMT61A reduced proliferation capacity in both 5637 and HT1197 cell lines. The average cell displacement of 5637 was also reduced upon TRMT6/TRMT61A depletion. Interestingly, TRMT6/TRMT61A depletion decreased mRNA expression of targets associated with the ATF6-branch of the UPR in 5637 but not in HT1197. Moreover, cell survival after induction of cellular stress was compromised after TRMT6/TRMT61A knockdown in 5637 but not in HT1197 cells.
Conclusion: The findings suggest that TRMT6/TRMT61A plays an oncogenic role in BLCA and is involved in desensitizing BLCA cells against cellular stress. Further investigation into the regulation of TRMT6/TRMT61A expression and its impact on cellular stress tolerance may provide insights for future BLCA treatment.
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http://dx.doi.org/10.3389/fonc.2023.1334112 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Chinese Academy of Sciences Key Laboratory of Tropical Marine Bio Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, Guangdong Provincial Observation and Research Station for Coastal Upwelling Ecosystem, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 511458, China.
Rotation of the bacterial flagellum, the first identified biological rotary machine, is driven by its stator units. Knowledge gained about the function of stator units has increasingly led to studies of rotary complexes in different cellular pathways. Here, we report that a tetrameric PilZ family protein, FlgX, is a structural component underneath the stator units in the flagellar motor of .
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Ministry of Education Key Laboratory of Environment Remediation and Ecological Health, Zhejiang Provincial Key Laboratory of Agricultural Resources and Environment, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
While iron (Fe) is essential for life and plays important roles for almost all growth related processes, it can trigger cell death in both animals and plants. However, the underlying mechanisms for Fe-induced cell death in plants remain largely unknown. S-nitrosoglutathione reductase (GSNOR) has previously been reported to regulate nitric oxide homeostasis to prevent Fe-induced cell death within root meristems.
View Article and Find Full Text PDFPLoS Comput Biol
January 2025
IRSD-Institut de Recherche en Santé Digestive, Université de Toulouse, INSERM, INRAE, ENVT, UPS, Toulouse, France.
Understanding the interplay between biology and mechanics in tissue architecture is challenging, particularly in terms of 3D tissue organization. Addressing this challenge requires a biological model enabling observations at multiple levels from cell to tissue, as well as theoretical and computational approaches enabling the generation of a synthetic model that is relevant to the biological model and allowing for investigation of the mechanical stresses experienced by the tissue. Using a monolayer human colon epithelium organoid as a biological model, freely available tools (Fiji, Cellpose, Napari, Morphonet, or Tyssue library), and the commercially available Abaqus FEM solver, we combined vertex and FEM approaches to generate a comprehensive viscoelastic finite element model of the human colon organoid and demonstrated its flexibility.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Key Laboratory of Mental Disorders, The Second Hospital of Shandong University, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, 250012, China.
Major depressive disorder (MDD) is usually considered associate with immune inflammation and synaptic injury within specific brain regions. However, the molecular mechanisms underlying the neural deterioration resulting in depression remain unclear. Here, it is found that miR-204-5p is markedly downregulated in the ventromedial prefrontal cortex (vmPFC) in a chronic unpredictable mild stress (CUMS) induce rat model of depression.
View Article and Find Full Text PDFMedicine (Baltimore)
January 2025
Opthalmology, Chongqing Hechuan District People's Hospital, Chongqing, China.
Background: Bushen-Huoxue-Mingmu-Formula (MMF) has achieved definite clinical efficacy. However, its mechanism is still unclear.
Objective: Investigating the molecular mechanism of MMF to protect retinal ganglion cells (RGCs).
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