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磷酸葡萄糖变位酶1通过调节PI3K/AKT信号通路抑制结肠癌细胞的迁移和侵袭。

PGM1 suppresses colorectal cancer cell migration and invasion by regulating the PI3K/AKT pathway.

作者信息

Zheng Zhewen, Zhang Xue, Bai Jian, Long Long, Liu Di, Zhou Yunfeng

机构信息

Department of Radiation Oncology and Medical Oncology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuchang District, Wuhan, Hubei, People's Republic of China.

Department of General Practice, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.

出版信息

Cancer Cell Int. 2022 May 25;22(1):201. doi: 10.1186/s12935-022-02545-7.

Abstract

BACKGROUND

Phosphoglucomutase 1 (PGM1) is known for its involvement in cancer pathogenesis. However, its biological role in colorectal cancer (CRC) has remained unknown. Here, we studied the functions and mechanisms of PGM1 in CRC.

METHODS

We verified PGM-1 as a differentially expressed gene (DEG) by employing a comprehensive strategy of TCGA-COAD dataset mining and computational biology. Relative levels of PGM-1 in CRC tumors and adjoining peritumoral tissues were determined by qRT-PCR, western blotting (WB), and immunohistochemical (IHC) staining in a tissue microarray. PGM1 functions were analyzed by CCK8, EdU, colony formation, cell cycle, apoptosis, and Transwell migration and invasion assays. The influence of PGM1 was further investigated by studying tumor formation in vivo.

RESULTS

The levels of PGM1 mRNA and protein were both reduced in CRC tissues, and the reductions were related to CRC pathology and overall survival. PGM1 knockdown stimulated both cell proliferation and colony formation, and inhibited cell cycle arrest and apoptosis, while overexpression of PGM1 produced the opposite effects in CRC cells both in vivo and in vitro. Furthermore, the effects of PGM1 were related to the PI3K/ AKT pathway.

CONCLUSION

We verified that PGM1 suppresses CRC progression via the PI3K/AKT pathway. These results suggest the potential for targeting PGM1 in treatment of CRC.

摘要

背景

磷酸葡萄糖变位酶1(PGM1)因其参与癌症发病机制而闻名。然而,其在结直肠癌(CRC)中的生物学作用仍不清楚。在此,我们研究了PGM1在CRC中的功能和机制。

方法

我们通过采用TCGA-COAD数据集挖掘和计算生物学的综合策略,验证PGM-1为差异表达基因(DEG)。通过qRT-PCR、蛋白质印迹法(WB)和组织芯片中的免疫组织化学(IHC)染色,测定CRC肿瘤及相邻瘤周组织中PGM-1的相对水平。通过CCK8、EdU、集落形成、细胞周期、凋亡以及Transwell迁移和侵袭试验分析PGM1的功能。通过研究体内肿瘤形成进一步探讨PGM1的影响。

结果

CRC组织中PGM1 mRNA和蛋白质水平均降低,且降低与CRC病理和总生存期相关。PGM1敲低刺激细胞增殖和集落形成,并抑制细胞周期停滞和凋亡,而PGM1过表达在体内和体外对CRC细胞产生相反的作用。此外,PGM1的作用与PI3K/AKT通路有关。

结论

我们证实PGM1通过PI3K/AKT通路抑制CRC进展。这些结果表明靶向PGM1治疗CRC的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c4d/9134613/45aab1c77c77/12935_2022_2545_Fig1_HTML.jpg

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