Differential transcription of the clusterin (CLU) gene yields two CLU isoforms, a nuclear form (nCLU) and a secretory form (sCLU), which play crucial roles in prostate tumorigenesis. Pro-apoptotic nCLU and anti-apoptotic sCLU have opposite effects and are differentially expressed in normal and cancer cells; however, their regulatory mechanisms at the transcriptional level are not yet known. Here, we examined the transcriptional regulation of nCLU in response to hypoxia. We identified three putative hypoxia response elements (HREs) in the human CLU promoter between positions -806 and +51 bp. Using a luciferase reporter, electrophoretic gel mobility shift, and chromatin immunoprecipitation assays, we further showed that hypoxia-inducible factor-1α (HIF-1α) bound directly to these sites and activated transcription. Exposure to the hypoxiamimetic compound CoCl₂, incubation under 1% O₂ conditions, or overexpression of HIF-1α enhanced nCLU expression and induced apoptosis in human prostate cancer PC3M cells. However, LNCaP prostate cancer cells were resistant to hypoxia-induced cell death. Methylation-specific PCR analysis revealed that the CLU promoter in PC3M cells was not methylated; in contrast, the CLU promoter in LNCap cells was methylated. Co-treatment of LNCaP cells with CoCl₂ and a demethylating agent promoted apoptotic cell death through the induction of nCLU. We conclude that nCLU expression is regulated by direct binding of HIF-1α to HRE sites and is epigenetically controlled by methylation of its promoter region.
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http://dx.doi.org/10.14348/molcells.2014.2349 | DOI Listing |
Int J Mol Sci
October 2024
The Anhui Provincial Key Laboratory of Biodiversity Conservation and Ecological Security in the Yangtze River Basin, College of Life Science, Anhui Normal University, Wuhu 241000, China.
The gene superfamily is widely distributed among higher eukaryotes and plays a significant role in numerous biological processes. However, there is limited knowledge about the structure and function of genes in the critically endangered species , which is endemic to China. A total of 170 genes were identified from the genome, classified into 13 families, and unevenly distributed across 16 chromosomes.
View Article and Find Full Text PDFMol Med
July 2024
Department of Urology, Affiliated Hospital of Guizhou Medical University, Clinical Medical College of Guizhou Medical University, No.28 Guiyi Street, Yunyan District, Guiyang, Guizhou Province, 550004, China.
Background: Diabetes mellitus (DM)-induced testicular damage is associated with sexual dysfunction and male infertility in DM patients. However, the pathogenesis of DM-induced testicular damage remains largely undefined.
Methods: A streptozotocin (STZ)-induced diabetic model and high glucose (HG)-treated in vitro diabetic model were established.
Biochim Biophys Acta Gene Regul Mech
December 2023
School of Biological Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, P.O. Bhimpur-Padanpur, Jatni, Khurda, Odisha, 752050, India; Homi Bhabha National Institute (HBNI), Training School Complex, Anushaktinagar, Mumbai, 400094, India. Electronic address:
Pseudoexfoliation (PEX) is a multifactorial age-related disease characterized by the deposition of extracellular fibrillar aggregates in the anterior ocular tissues. This study aims to identify the genetic and epigenetic contribution of clusterin (CLU) in PEX pathology. CLU is a molecular chaperone upregulated in PEX and genetically associated with the disease.
View Article and Find Full Text PDFMicroorganisms
May 2023
Biotechnology Program, Center for Sustainable Development, College of Art and Sciences, Qatar University, Doha P.O. Box 2713, Qatar.
Abiotic and biotic stresses such as salt stress and fungal infections significantly affect plant growth and productivity, leading to reduced crop yield. Traditional methods of managing stress factors, such as developing resistant varieties, chemical fertilizers, and pesticides, have shown limited success in the presence of combined biotic and abiotic stress factors. Halotolerant bacteria found in saline environments have potential as plant promoters under stressful conditions.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
January 2023
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Purpose: This study aimed to investigate the role and molecular mechanism of ETS1 in the proliferation and differentiation of human limbal epithelial stem cells (LESCs).
Methods: RNA-seq and quantitative real-time PCR were used to determine gene expression changes when ETS1 and HMGA2 was knocked down using short-hairpin RNAs or overexpressed by lentivirus. Immunofluorescence and flow cytometry experiments were performed to assess the roles of ETS1 and HMGA2 in LESC proliferation.
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