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MAGT1 is required for HeLa cell proliferation through regulating p21 expression, S-phase progress, and ERK/p38 MAPK MYC axis
Cell Cycle ( IF 3.4 ) Pub Date : 2021-09-09 , DOI: 10.1080/15384101.2021.1974792
Caili Bi 1, 2, 3 , Xue Zhang 1, 4 , Yueyue Chen 1, 2 , Yushuo Dong 1 , Yixin Shi 1 , Yunshen Lei 1 , Dan Lv 5 , Xiaowei Cao 1, 6 , Wei Li 1, 2 , Hongcan Shi 1, 2
Affiliation  

ABSTRACT

Magnesium transporter subtype 1 (MAGT1) is known to participate in animal development and cell differentiation. Thus far, MAGT1 studies have mainly focused on its role in cardiomyocyte regulation and differentiation; only a few studies have demonstrated its role in cell proliferation. To investigate the underlying mechanism of MAGT1 in cell proliferation, HeLa and SiHa cells were transiently knocked down with different siRNAs. We showed that cell proliferation was substantially restricted by S-phase arrest and apoptosis in the MAGT1-knocked down cells, which was further confirmed by the increased expression of p21, cyclin-A1, and cyclin-B1, as well as the decreased expression of MYC, cyclin-D1, cyclin-E1, and CDK2. MAGT1 knockdown also resulted in significant changes in the transcriptional expression of 1,598 genes that were analyzed by RNA sequencing. Bioinformatics analysis showed that MAGT1 was related to the MAPK signaling pathway. Western blot analysis confirmed that the phosphorylation of extracellular signal-related protein kinase 1/2 (ERK1/2) and p38 was remarkably reduced in MAGT1 down-regulated groups. Additionally, MAGT1 was required for the function of viral proteins E6/E7 during cell proliferation and G1/S cell-cycle progression. Therefore, MAGT1 plays a crucial role in the proliferation of HPV-positive cervical cancer cells, S-phase progression, and the ERK/p38 MAPK signaling pathway. These results indicate the potential of MAGT1 as a novel target for anticancer research.

Abbreviations: MAGT1: Magnesium transporter subtype 1; MAPK: Mitogen-activated protein kinase; XMEN: X-linked immunodeficiency with Magnesium defect, Epstein-Barr virus infection and Neoplasia; BMMSCs: Bone Marrow Mesenchymal Stem Cells; Dpp: Decapentaplegic; CDKIs: CDK inhibitors; GPCR: G-protein coupled receptor; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; RTK: Receptor Tyrosine Kinase; PTK: Protein Tyrosine Kinase; FGFR: Fibroblast Growth Factor Receptor; BMP: Bone Morphogenetic Protein; HPV18 E6/E7: Human Papillomavirus 18 Early protein 6/ early protein 7; FACS: Fluorescence Activated Cell Sorting; PI: Propidium Iodide



中文翻译:

MAGT1 通过调节 p21 表达、S 期进展和 ERK/p38 MAPK MYC 轴是 HeLa 细胞增殖所必需的

摘要

已知镁转运蛋白亚型 1 (MAGT1) 参与动物发育和细胞分化。迄今为止,MAGT1的研究主要集中在其在心肌细胞调节和分化中的作用。只有少数研究证明了它在细胞增殖中的作用。为了研究 MAGT1 在细胞增殖中的潜在机制,HeLa 和 SiHa 细胞被不同的 siRNA 瞬时击倒。我们发现,在 MAGT1 敲低的细胞中,细胞增殖受到 S 期阻滞和凋亡的显着限制,这进一步通过 p21、cyclin-A1 和 cyclin-B1 的表达增加以及MYC、cyclin-D1、cyclin-E1 和 CDK2。MAGT1 敲低还导致 1 的转录表达发生显着变化,通过 RNA 测序分析了 598 个基因。生物信息学分析表明,MAGT1与MAPK信号通路有关。蛋白质印迹分析证实,在 MAGT1 下调组中,细胞外信号相关蛋白激酶 1/2 (ERK1/2) 和 p38 的磷酸化显着降低。此外,在细胞增殖和 G1/S 细胞周期进程中,病毒蛋白 E6/E7 的功能需要 MAGT1。因此,MAGT1 在 HPV 阳性宫颈癌细胞的增殖、S 期进展和 ERK/p38 MAPK 信号通路中起着至关重要的作用。这些结果表明 MAGT1 作为抗癌研究的新靶点的潜力。蛋白质印迹分析证实,在 MAGT1 下调组中,细胞外信号相关蛋白激酶 1/2 (ERK1/2) 和 p38 的磷酸化显着降低。此外,在细胞增殖和 G1/S 细胞周期进程中,病毒蛋白 E6/E7 的功能需要 MAGT1。因此,MAGT1 在 HPV 阳性宫颈癌细胞的增殖、S 期进展和 ERK/p38 MAPK 信号通路中起着至关重要的作用。这些结果表明 MAGT1 作为抗癌研究的新靶点的潜力。蛋白质印迹分析证实,在 MAGT1 下调组中,细胞外信号相关蛋白激酶 1/2 (ERK1/2) 和 p38 的磷酸化显着降低。此外,在细胞增殖和 G1/S 细胞周期进程中,病毒蛋白 E6/E7 的功能需要 MAGT1。因此,MAGT1 在 HPV 阳性宫颈癌细胞的增殖、S 期进展和 ERK/p38 MAPK 信号通路中起着至关重要的作用。这些结果表明 MAGT1 作为抗癌研究的新靶点的潜力。MAGT1 在 HPV 阳性宫颈癌细胞增殖、S 期进展和 ERK/p38 MAPK 信号通路中起关键作用。这些结果表明 MAGT1 作为抗癌研究的新靶点的潜力。MAGT1 在 HPV 阳性宫颈癌细胞增殖、S 期进展和 ERK/p38 MAPK 信号通路中起关键作用。这些结果表明 MAGT1 作为抗癌研究的新靶点的潜力。

缩写:MAGT1:镁转运蛋白亚型 1;MAPK:丝裂原活化蛋白激酶;XMEN:X连锁免疫缺陷伴镁缺陷、爱泼斯坦-巴尔病毒感染和肿瘤;BMMSCs:骨髓间充质干细胞;民进党:脑瘫;CDKIs:CDK抑制剂;GPCR:G蛋白偶联受体;GO:基因本体;KEGG:京都基因和基因组百科全书;RTK:受体酪氨酸激酶;PTK:蛋白酪氨酸激酶;FGFR:成纤维细胞生长因子受体;BMP:骨形态发生蛋白;HPV18 E6/E7:人乳头瘤病毒 18 早期蛋白 6/早期蛋白 7;FACS:荧光激活细胞分选;PI:碘化丙啶

更新日期:2021-11-12
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