Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Feb;25(2):440-446.
doi: 10.1007/s12094-022-02956-y. Epub 2022 Oct 3.

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

Duo Xu #  1 , Meirong Li #  2 , Longyan Ran  1 , Xiaochen Li  1 , Xingwang Sun  2 , Tao Yin  3
Affiliations

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

Duo Xu et al. Clin Transl Oncol. 2023 Feb.

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.

Keywords: C5aR1; CRC; EMT; RNA-seq; Wnt/β-catenin.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Fig. 1
Fig. 1
The Bioinformatics analysis data. A The DEGs (SETDB1_G: overexpression group; SETDB1_S: knockdown group). B The DEGs were consistent with SETDB1 (SETDB1_G_UP: up-regulated genes in overexpressed group; SETDB1_S_DOWN: down-regulated genes in knockdown group). C–F GO and KEGG analysis of DEGs with SETDB1_G_UP group (C, D) and SETDB1_S_DOWN group (E, F). G A survival curve gained from HPA shows high expression of C5aR1 reduces survival of CRC patients (Low expression (n = 476), high expression (n = 121), p = 0.017)
Fig. 2
Fig. 2
The expression of C5aR1. A The expression of C5aR1 in CRC cell lines. B Transfection efficiency validation of HCT116. C Transfection efficiency validation of SW620. D Transfection efficiency validation of RKO
Fig. 3
Fig. 3
C5aR1 promotes tumorigenesis and metastasis of CRC cells in vitro. A–C CCK8 assay of C5aR1-silenced cells after transfected with siRNA C5aR1-1 and siRNA C5aR1-3 and control cells in HCT116 and SW620 cell lines (A–B) and overexpression of C5aR1 cells with plasmid and control cells in RKO cell line (C). D–F Wound healing assay of C5aR1-silenced cells after transfected with siRNA C5aR1-1 and siRNA C5aR1-3 and control cells in HCT116 and SW620 cell lines (D–E) and overexpression of C5aR1 cells with plasmid and control cells in RKO cell line (F). G–I Colony formation assay of C5aR1-silenced cells after transfected with siRNA C5aR1-1 and siRNA C5aR1-3 and control cells in HCT116 and SW620 cell lines (G–H) and overexpression of C5aR1 cells with plasmid and control cells in RKO cell line (I). J–L Transwell invasion assay of C5aR1-silenced cells after transfected with siRNA C5aR1-1 and siRNA C5aR1-3 and control cells in HCT116 and SW620 cell lines (J–K) and overexpression of C5aR1 cells with plasmid and control cells in RKO cell line (L)
Fig. 4
Fig. 4
The mechanism of C5aR1 influencing the development of colorectal cancer. A The expression of C5aR1 altered the molecular expression associated with EMT. B The expression of C5aR1 altered the molecular expression of key protein in the Wnt/β-catenin pathway
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Cao W, Chen HD, Yu YW, et al. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020 [J] Chin Med J. 2021;134(7):783–791. doi: 10.1097/CM9.0000000000001474. - DOI - PMC - PubMed
    1. Campos FG. Colorectal cancer in young adults: a difficult challenge [J] World J Gastroenterol. 2017;23(28):5041–5044. doi: 10.3748/wjg.v23.i28.5041. - DOI - PMC - PubMed
    1. Cao H, Xu E, Liu H, et al. Epithelial-mesenchymal transition in colorectal cancer metastasis: a system review [J] Pathol Res Pract. 2015;211(8):557–569. doi: 10.1016/j.prp.2015.05.010. - DOI - PubMed
    1. Chen K, Zhang F, Ding J, et al. Histone methyltransferase SETDB1 promotes the progression of colorectal cancer by inhibiting the expression of TP53 [J] J Cancer. 2017;8(16):3318–3330. doi: 10.7150/jca.20482. - DOI - PMC - PubMed
    1. Ryu TY, Kim K, Kim SK, et al. SETDB1 regulates SMAD7 expression for breast cancer metastasis [J] BMB Rep. 2019;52(2):139–144. doi: 10.5483/BMBRep.2019.52.2.235. - DOI - PMC - PubMed

MeSH terms