METTL1 promotes colorectal cancer cell proliferation by attenuating CHEK2-induced G1/S phase arrest.
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ABSTRACT:
SUBMITTER: Jiang H
PROVIDER: S-EPMC10491903 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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METTL1 promotes colorectal cancer cell proliferation by attenuating CHEK2-induced G1/S phase arrest.
Jiang Houxiang H Liu Ying Y Song Huibin H Xia Jinquan J Tian Ying Y Wang Luolin L Li Mingwei M Xu Zhenyu Z Xu Zhenglei Z Zou Chang C
Genes & diseases 20230518 2
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Project description:BackgroundDepletion of calcium (Ca2+) from the endoplasmic reticulum (ER) activates the ubiquitous store-operated Ca2+ entry (SOCE) pathway which sustains long-term Ca2+ signals and is critical for cellular functions. Stromal interacting molecule 1 (STIM1) serves a dual role as an ER Ca2+ sensor and activator of SOCE. Aberrant expression of STIM1 could be observed in several human cancer cells. However, the role of STIM1 in regulating tumorigenesis of human glioblastoma still remains unclear.MethodsExpression of STIM1 protein in a panel of human glioblastoma cell lines (U251, U87 and U373) in different transformation level were evaluated by Western blot method. STIM1 loss of function was performed on U251 cells, derived from grade IV astrocytomas-glioblastoma multiforme with a lentvirus-mediated short harpin RNA (shRNA) method. The biological impacts after knock down of STIM1 on glioblastoma cells were investigated in vitro and in vivo.ResultsWe discovered that STIM1 protein was expressed in U251, U87 and U373 cells, and especially higher in U251 cells. RNA interference efficiently downregulated the expression of STIM1 in U251 cells at both mRNA and protein levels. Specific downregulation of STIM1 inhibited U251 cell proliferation by inducing cell cycle arrest in G0/G1 phase through regulation of cell cycle-related genes, such as p21Waf1/Cip1, cyclin D1 and cyclin-dependent kinase 4 (CDK4), and the antiproliferative effect of STIM1 silencing was also observed in U251 glioma xenograft tumor model.ConclusionOur findings confirm STIM1 as a rational therapeutic target in human glioblastoma, and also indicate that lentivirus-mediated STIM1 silencing is a promising therapeutic strategy for human glioblastoma.
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2023-03-09 | PXD037143 | Pride
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