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RNA 结合蛋白 PUM1 促进结肠癌细胞的增殖和迁移。

RNA binding protein PUM1 promotes colon cancer cell proliferation and migration.

机构信息

Department of Genetic Engineering, School of Bio-Engineering, SRM Institute of Science and Technology, Kattankulathur, Kanchipuram 603203, Tamil Nadu, India.

Department of Biotechnology, School of Bio-Engineering, SRM Institute of Science and Technology, Kattankulathur, Kanchipuram 603203, Tamil Nadu, India.

出版信息

Int J Biol Macromol. 2021 Mar 31;174:549-561. doi: 10.1016/j.ijbiomac.2021.01.154. Epub 2021 Jan 25.

Abstract

Colon cancer is the third leading cause of death worldwide and sixth in India, where it is the cause of 5.8% of the total deaths. Pumilio-1 (PUM1) is an RNA binding protein whose regulatory role is by binding to the consensus 5'UGUANAUA3' sequence on the 3'UTR of the mRNA targets and post-transcriptionally repressing their expression. This study is the first of its kind to report the expression or function of PUM1 in colon cancer. We found that PUM1 mRNA expression is high in primary and metastatic colon cancer cell lines when compared to the normal colon cell line. Immunohistochemistry analysis showed similar trend wherein compared to the normal colon tissue, PUM1 was found to be overexpressed in both adenocarcinoma and in metastatic carcinoma. This confirms the role of PUM1 in colon cancer progression. PUM1 overexpression study in HCT116 revealed that cells transfected with PUM1 plasmid show an increased rate of proliferation, migration and colony formation. Overexpressing PUM1 increases the number and size of spheroids indicating the role of PUM1 in maintaining cancer stem cells. Overall, this is the first study that has shown the role of PUM1 in colon cancer development.

摘要

结肠癌是全球第三大死亡原因,在印度排名第六,占总死亡人数的 5.8%。Pumilio-1(PUM1)是一种 RNA 结合蛋白,其调节作用是通过与 mRNA 靶标 3'UTR 上的保守 5'UGUANAUA3'序列结合,从而抑制其转录后表达。这项研究是首次报道 PUM1 在结肠癌中的表达或功能。我们发现,与正常结肠细胞系相比,PUM1 mRNA 在原发性和转移性结肠癌细胞系中的表达较高。免疫组织化学分析显示出相似的趋势,与正常结肠组织相比,PUM1 在腺癌和转移性癌中均过度表达。这证实了 PUM1 在结肠癌进展中的作用。在 HCT116 中进行的 PUM1 过表达研究表明,转染 PUM1 质粒的细胞增殖、迁移和集落形成率增加。过表达 PUM1 增加了球体的数量和大小,表明 PUM1 在维持癌症干细胞中的作用。总的来说,这是第一项表明 PUM1 在结肠癌发生发展中的作用的研究。

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