STEAP3 promotes colon cancer cell proliferation and migration via regulating histone acetylation.

IF 3.8 2区 生物学 Q2 GENETICS & HEREDITY Human Genetics Pub Date : 2024-03-01 Epub Date: 2024-03-13 DOI:10.1007/s00439-024-02646-5
Jinjuan Lv, Xiaoqian Liu, Zhiwei Sun, Jianfeng Gao, Xiaoqi Yu, Mengyan Zhang, Zhenyu Zhang, Shuangyi Ren, Yunfei Zuo
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Abstract

Colorectal cancer (CRC) is the third most prevalent diagnosed cancer in men and second most prevalent cancer in women. H3K27ac alterations are more commonly than gene mutations in colorectal cancer. Most colorectal cancer genes have significant H3K27ac changes, which leads to an over-expression disorder in gene transcription. Over-expression of STEAP3 is involved in a variety of tumors, participating in the regulation of cancer cell proliferation and migration. The purpose of this work is to investigate the role of STEAP3 in the regulation of histone modification (H3K27ac) expression in colon cancer. Bioinformatic ChIP-seq, ChIP-qPCR and ATAC-seq were used to analyze the histone modification properties and gene accessibility of STEAP3. Western blot and qRT-PCR were used to evaluate relative protein and gene expression, respectively. CRISPR/Cas9 technology was used to knockout STEAP3 on colon cancer cells to analyze the effect of ATF3 on STEAP3. STEAP3 was over-expressed in colon cancer and associated with higher metastases and more invasive and worse stage of colon cancer. ChIP-seq and ChIP-qPCR analyses revealed significant enrichment of H3K27ac in the STEAP3 gene. In addition, knocking down STEAP3 significantly inhibits colon cancer cell proliferation and migration and down-regulates H3K27ac expression. ChIP-seq found that ATF3 is enriched in the STEAP3 gene and CRISPR/Cas9 technology used for the deletion of the ATF3 binding site suppresses the expression of STEAP3. Over-expression of STEAP3 promotes colon cancer cell proliferation and migration. Mechanical studies have indicated that H3K27ac and ATF3 are significantly enriched in the STEAP3 gene and regulate the over-expression of STEAP3.

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STEAP3 通过调节组蛋白乙酰化促进结肠癌细胞的增殖和迁移。
结肠直肠癌(CRC)是男性第三大、女性第二大确诊癌症。在结直肠癌中,H3K27ac 改变比基因突变更为常见。大多数结直肠癌基因都有明显的 H3K27ac 变化,从而导致基因转录过度表达紊乱。STEAP3 的过度表达涉及多种肿瘤,参与调控癌细胞的增殖和迁移。本研究旨在探讨 STEAP3 在结肠癌组蛋白修饰(H3K27ac)表达调控中的作用。生物信息学 ChIP-seq、ChIP-qPCR 和 ATAC-seq 用于分析 STEAP3 的组蛋白修饰特性和基因可及性。Western 印迹和 qRT-PCR 分别用于评估蛋白质和基因的相对表达。利用 CRISPR/Cas9 技术敲除结肠癌细胞中的 STEAP3,分析 ATF3 对 STEAP3 的影响。STEAP3在结肠癌中过度表达,与结肠癌的高转移率、高侵袭性和严重分期有关。ChIP-seq 和 ChIP-qPCR 分析显示,STEAP3 基因中的 H3K27ac 显著富集。此外,敲除 STEAP3 能显著抑制结肠癌细胞的增殖和迁移,并下调 H3K27ac 的表达。ChIP-seq 发现 ATF3 在 STEAP3 基因中富集,利用 CRISPR/Cas9 技术删除 ATF3 结合位点可抑制 STEAP3 的表达。过度表达 STEAP3 会促进结肠癌细胞的增殖和迁移。力学研究表明,H3K27ac 和 ATF3 在 STEAP3 基因中显著富集,并调控 STEAP3 的过度表达。
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来源期刊
Human Genetics
Human Genetics 生物-遗传学
CiteScore
10.80
自引率
3.80%
发文量
94
审稿时长
1 months
期刊介绍: Human Genetics is a monthly journal publishing original and timely articles on all aspects of human genetics. The Journal particularly welcomes articles in the areas of Behavioral genetics, Bioinformatics, Cancer genetics and genomics, Cytogenetics, Developmental genetics, Disease association studies, Dysmorphology, ELSI (ethical, legal and social issues), Evolutionary genetics, Gene expression, Gene structure and organization, Genetics of complex diseases and epistatic interactions, Genetic epidemiology, Genome biology, Genome structure and organization, Genotype-phenotype relationships, Human Genomics, Immunogenetics and genomics, Linkage analysis and genetic mapping, Methods in Statistical Genetics, Molecular diagnostics, Mutation detection and analysis, Neurogenetics, Physical mapping and Population Genetics. Articles reporting animal models relevant to human biology or disease are also welcome. Preference will be given to those articles which address clinically relevant questions or which provide new insights into human biology. Unless reporting entirely novel and unusual aspects of a topic, clinical case reports, cytogenetic case reports, papers on descriptive population genetics, articles dealing with the frequency of polymorphisms or additional mutations within genes in which numerous lesions have already been described, and papers that report meta-analyses of previously published datasets will normally not be accepted. The Journal typically will not consider for publication manuscripts that report merely the isolation, map position, structure, and tissue expression profile of a gene of unknown function unless the gene is of particular interest or is a candidate gene involved in a human trait or disorder.
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