CPEB2 inhibit cell proliferation through upregulating p21 mRNA stability in glioma.

CPEB2 inhibit cell proliferation through upregulating p21 mRNA stability in glioma.
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DOI:
10.1038/s41598-023-50848-0
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发表时间:
2023-12-29
期刊:
影响因子:
4.6
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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脑胶质瘤是成人最常见的原发性恶性脑肿瘤,目前仍是一种无法治愈的疾病。因此,迫切需要寻找新的控制胶质瘤进展的分子机制,以作为胶质瘤患者的治疗靶点。RNA结合蛋白质多聚腺苷酸元件结合蛋白2(CPEB 2)参与多种肿瘤的发病机制。然而,CPEB 2在胶质瘤进展中的作用尚不清楚。本研究采用一系列生物学和细胞学方法,在体外和体内研究了CPEB 2在胶质瘤中的作用及其分子机制。我们的工作表明CPEB2在各种胶质瘤患者队列中显著下调。通过过表达和敲低CPEB 2的功能表征揭示其抑制胶质瘤细胞增殖并促进凋亡。CPEB 2通过增加胶质瘤中p21 mRNA的稳定性和诱导G1细胞周期阻滞来发挥抗肿瘤作用。总之,本研究首次报道了CPEB 2下调并参与胶质瘤的发病机制,并通过靶向p21在胶质瘤中鉴定了CPEB 2作为一个重要的抑癌基因,提示CPEB 2可能成为胶质瘤患者预后的一个有前景的预测生物标志物。
Glioma is the most common primary malignant brain tumor in adults and remains an incurable disease at present. Thus, there is an urgent need for progress in finding novel molecular mechanisms that control the progression of glioma which could be used as therapeutic targets for glioma patients. The RNA binding protein cytoplasmic polyadenylate element-binding protein 2 (CPEB2) is involved in the pathogenesis of several tumors. However, the role of CPEB2 in glioma progression is unknown. In this study, the functional characterization of the role and molecular mechanism of CPEB2 in glioma were examined using a series of biological and cellular approaches in vitro and in vivo. Our work shows CPEB2 is significantly downregulated in various glioma patient cohorts. Functional characterization of CPEB2 by overexpression and knockdown revealed that it inhibits glioma cell proliferation and promotes apoptosis. CPEB2 exerts an anti-tumor effect by increasing p21 mRNA stability and inducing G1 cell cycle arrest in glioma. Overall, this work stands as the first report of CPEB2 downregulation and involvement in glioma pathogenesis, and identifies CPEB2 as an important tumor suppressor gene through targeting p21 in glioma, which revealed that CPEB2 may become a promising predictive biomarker for prognosis in glioma patients.
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