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C5aR1 通过 EMT 促进结直肠癌的进展,并激活 Wnt/β-catenin 通路。

C5aR1 promotes the progression of colorectal cancer by EMT and activating Wnt/β-catenin pathway.

机构信息

College of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, China.

Department of Pathology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.

出版信息

Clin Transl Oncol. 2023 Feb;25(2):440-446. doi: 10.1007/s12094-022-02956-y. Epub 2022 Oct 3.

Abstract

BACKGROUND

Colorectal cancer (CRC) is one of the most common malignant cancers in human, and its incidence increases gradually every year. Metastasis is an important factor leading to tumor development. The epithelial-mesenchymal transition (EMT) has been proved to be closely related to tumor metastasis, yet its related mechanism in CRC remains to be explored.

METHODS

We obtained the differentially expressed gene C5aR1 with SETDB1 stable overexpression and knockdown cells by RNA-seq. Cell proliferation was tested by CCK8 and colony formation assay. Migration and invasion of CRC cells were determined by the wound healing and transwell invasion assay. The potential pathway of C5aR1 in CRC was preliminarily studied by western blotting.

RESULTS

Sequencing results showed that C5aR1 was the most differentially expressed gene. By changing the expression of C5aR1 in CRC cells, this study found that C5aR1 promoted the proliferation, colony formation, migration and invasion of CRC cells in vitro. C5aR1 accelerated the EMT process and the expression of C5aR1 altered the molecular expression of key proteins in the Wnt/β-catenin pathway.

CONCLUSION

C5aR1 promotes the development of CRC and accelerates the EMT process. Furthermore, C5aR1 may involve in the regulation of Wnt/β-catenin pathway in CRC.

摘要

背景

结直肠癌(CRC)是人类最常见的恶性肿瘤之一,其发病率逐年逐渐增加。转移是导致肿瘤发展的重要因素。上皮-间充质转化(EMT)已被证明与肿瘤转移密切相关,但 CRC 中其相关机制仍待探索。

方法

我们通过 RNA-seq 获得了 SETDB1 稳定过表达和敲低细胞中差异表达的基因 C5aR1。通过 CCK8 和集落形成实验检测细胞增殖。通过划痕愈合和 Transwell 侵袭实验测定 CRC 细胞的迁移和侵袭能力。通过 Western blot 初步研究了 C5aR1 在 CRC 中的潜在途径。

结果

测序结果表明 C5aR1 是表达差异最显著的基因。通过改变 CRC 细胞中 C5aR1 的表达,本研究发现 C5aR1 促进了 CRC 细胞在体外的增殖、集落形成、迁移和侵袭。C5aR1 加速了 EMT 过程,并且 C5aR1 的表达改变了 Wnt/β-catenin 通路中关键蛋白的分子表达。

结论

C5aR1 促进 CRC 的发展并加速 EMT 过程。此外,C5aR1 可能参与 CRC 中 Wnt/β-catenin 通路的调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0106/9873742/aaa69d580e67/12094_2022_2956_Fig1_HTML.jpg

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