CSGALNACT2 restricts ovarian cancer migration and invasion by modulating MAPK/ERK pathway through DUSP1

IF 6.6 2区医学 Q1 Medicine

Cellular Oncology Pub Date : 2023-12-12 DOI:10.1007/s13402-023-00903-9

Mingjun Ma, Chao Wang, Meixuan Wu, Sijia Gu, Jiani Yang, Yue Zhang, Shanshan Cheng, Shilin Xu, Minghai Zhang, Yongsong Wu, Yaqian Zhao, Xiu Tian, Dominic Chih-Cheng Voon, Chiaki Takahashi, Jindan Sheng, Yu Wang

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引用次数: 0

Abstract

Purpose

Ovarian cancer is one of the leading causes of cancer-related death among women. CSGALNACT2 is a vital Golgi transferase and is related to a variety of human diseases. However, its expression pattern and function in ovarian cancer remain uncertain.

Methods

The Cancer Genome Atlas and GEPIA databases were used to assess the expression of CSGALNACT2 in ovarian cancer patients. RNA-seq, qRT-PCR, and IHC were used to verify the expression of CSGALNACT2 in ovarian cancer tissues. Then, in vivo and in vitro experiments were conducted to evaluate the role of CSGALNACT2 in the progression of ovarian cancer. RNA-seq and GSEA were used to reveal the potential biological function and oncogenic pathways of CSGALNACT2.

Results

We demonstrated that the mRNA expression and protein level of CSGALNACT2 were significantly downregulated in ovarian cancer and ovarian cancer metastatic tissues. CSGALNACT2 can significantly inhibit the migration, invasion, and clonogenic growth of ovarian cancer in vitro and is progressively lost during ovarian cancer progression in vivo. CSGALNACT2 suppresses ovarian cancer migration and invasion via DUSP1 modulation of the MAPK/ERK pathway through RNA-seq, KEGG analysis, and Western blotting. Moreover, CSGALNACT2 expression was correlated with immune cell infiltration and had prognostic value in different immune cell-enriched or decreased ovarian cancer. In addition, patients with CSGALNACT2 downregulation are less likely to benefit from immunotherapy.

Conclusion

As an ovarian cancer suppressor gene, CSGALNACT2 inhibits the development of ovarian cancer, and it might be used as a prognostic biomarker in patients with ovarian cancer.

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CSGALNACT2 通过 DUSP1 调节 MAPK/ERK 通路，从而限制卵巢癌的迁移和侵袭

目的卵巢癌是女性癌症相关死亡的主要原因之一。CSGALNACT2 是一种重要的高尔基体转移酶，与多种人类疾病相关。方法利用癌症基因组图谱和 GEPIA 数据库评估 CSGALNACT2 在卵巢癌患者中的表达。采用 RNA-seq、qRT-PCR 和 IHC 验证 CSGALNACT2 在卵巢癌组织中的表达。然后，通过体内和体外实验评估 CSGALNACT2 在卵巢癌进展中的作用。结果表明，在卵巢癌和卵巢癌转移组织中，CSGALNACT2的mRNA表达和蛋白水平均显著下调。CSGALNACT2在体外能明显抑制卵巢癌的迁移、侵袭和克隆性生长，在体内卵巢癌进展过程中会逐渐消失。通过RNA-seq、KEGG分析和Western印迹，CSGALNACT2通过DUSP1调节MAPK/ERK通路抑制卵巢癌的迁移和侵袭。此外，CSGALNACT2的表达与免疫细胞浸润相关，在不同免疫细胞富集或减少的卵巢癌中具有预后价值。结论作为一种卵巢癌抑制基因，CSGALNACT2能抑制卵巢癌的发展，可作为卵巢癌患者的预后生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research

CiteScore

10.40

自引率

1.50%

发文量

审稿时长

16 weeks

期刊介绍： The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.