Clonorchis sinensis Granulin Promotes Malignant Transformation of Hepatocyte Through EGFR-Mediated RAS/MAPK/ERK and PI3K/Akt Signaling Pathways
The biological functions of growth factor, such as granulins, have been explored in parasites, and we elucidated that Clonorchis sinensis granulin (CsGRN) promoted the metastasis of hepatocellular carcinoma in our previous study. However, it is still unclear for the malignant transformation role of...
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2021
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oai:doaj.org-article:782eb554ac32426b83386b955d6316932021-11-10T05:48:46ZClonorchis sinensis Granulin Promotes Malignant Transformation of Hepatocyte Through EGFR-Mediated RAS/MAPK/ERK and PI3K/Akt Signaling Pathways2235-298810.3389/fcimb.2021.734750https://doaj.org/article/782eb554ac32426b83386b955d6316932021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.734750/fullhttps://doaj.org/toc/2235-2988The biological functions of growth factor, such as granulins, have been explored in parasites, and we elucidated that Clonorchis sinensis granulin (CsGRN) promoted the metastasis of hepatocellular carcinoma in our previous study. However, it is still unclear for the malignant transformation role of CsGRN in normal human hepatocytes. In this study, by transfecting pEGFP-C1-CsGRN eukaryotic expression plasmid, a cell line with stable overexpression of CsGRN in normal hepatocyte (LO2-GRN cells) was constructed. The effects on cell proliferation were detected by carrying out cell counting kit-8 (CCK8) assay and colony formation assay. Additionally, we conducted flow cytometry analysis to determine whether the proliferation of CsGRN was due to cell cycle arrest. Subsequently, the migration ability and the invasion ability of LO2-GRN cells were evaluated through wound-healing assay and transwell assay. Meanwhile, the levels of the markers of RAS/MAPK/ERK and PI3K/Akt signaling pathways activation in LO2-GRN cells were assessed by quantitative RT-PCR and Western blot. Our results indicated that CsGRN promoted the proliferation of LO2 cells by regulating the expression of cell-cycle-related genes. Moreover, the overexpression of CsGRN regulates malignant metastasis of liver cells by inducing the upregulation of epithelial–mesenchymal transition (EMT) marker proteins. Furthermore, both mRNA and protein expression levels of p-EGFR, RAS, p-ERK, p-AKT, p-PI3K, and p-braf have been enhanced by CsGRN. These results showed that CsGRN promoted the malignant transformation of hepatocytes by regulating epidermal growth factor receptor (EGFR)-mediated RAS/MAPK/ERK and PI3K/Akt signaling pathways, which suggested that CsGRN could serve as a novel oncoprotein during Clonorchis sinensis–associated malignant transformation of hepatocytes.Caiqin WangCaiqin WangCaiqin WangCaiqin WangCaiqin WangQing HeQing HeQing HeQing HeYingxuan YinYingxuan YinYingxuan YinYingxuan YinYinjuan WuYinjuan WuYinjuan WuYinjuan WuXuerong LiXuerong LiXuerong LiXuerong LiFrontiers Media S.A.articleClonorchis sinensis granulin (CsGRN)hepatocytemalignant transformationRAS/MAPK/ERK signaling pathwaysPI3K/Akt signaling pathwaysMicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021) |
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Clonorchis sinensis granulin (CsGRN) hepatocyte malignant transformation RAS/MAPK/ERK signaling pathways PI3K/Akt signaling pathways Microbiology QR1-502 |
| spellingShingle |
Clonorchis sinensis granulin (CsGRN) hepatocyte malignant transformation RAS/MAPK/ERK signaling pathways PI3K/Akt signaling pathways Microbiology QR1-502 Caiqin Wang Caiqin Wang Caiqin Wang Caiqin Wang Caiqin Wang Qing He Qing He Qing He Qing He Yingxuan Yin Yingxuan Yin Yingxuan Yin Yingxuan Yin Yinjuan Wu Yinjuan Wu Yinjuan Wu Yinjuan Wu Xuerong Li Xuerong Li Xuerong Li Xuerong Li Clonorchis sinensis Granulin Promotes Malignant Transformation of Hepatocyte Through EGFR-Mediated RAS/MAPK/ERK and PI3K/Akt Signaling Pathways |
| description |
The biological functions of growth factor, such as granulins, have been explored in parasites, and we elucidated that Clonorchis sinensis granulin (CsGRN) promoted the metastasis of hepatocellular carcinoma in our previous study. However, it is still unclear for the malignant transformation role of CsGRN in normal human hepatocytes. In this study, by transfecting pEGFP-C1-CsGRN eukaryotic expression plasmid, a cell line with stable overexpression of CsGRN in normal hepatocyte (LO2-GRN cells) was constructed. The effects on cell proliferation were detected by carrying out cell counting kit-8 (CCK8) assay and colony formation assay. Additionally, we conducted flow cytometry analysis to determine whether the proliferation of CsGRN was due to cell cycle arrest. Subsequently, the migration ability and the invasion ability of LO2-GRN cells were evaluated through wound-healing assay and transwell assay. Meanwhile, the levels of the markers of RAS/MAPK/ERK and PI3K/Akt signaling pathways activation in LO2-GRN cells were assessed by quantitative RT-PCR and Western blot. Our results indicated that CsGRN promoted the proliferation of LO2 cells by regulating the expression of cell-cycle-related genes. Moreover, the overexpression of CsGRN regulates malignant metastasis of liver cells by inducing the upregulation of epithelial–mesenchymal transition (EMT) marker proteins. Furthermore, both mRNA and protein expression levels of p-EGFR, RAS, p-ERK, p-AKT, p-PI3K, and p-braf have been enhanced by CsGRN. These results showed that CsGRN promoted the malignant transformation of hepatocytes by regulating epidermal growth factor receptor (EGFR)-mediated RAS/MAPK/ERK and PI3K/Akt signaling pathways, which suggested that CsGRN could serve as a novel oncoprotein during Clonorchis sinensis–associated malignant transformation of hepatocytes. |
| format |
article |
| author |
Caiqin Wang Caiqin Wang Caiqin Wang Caiqin Wang Caiqin Wang Qing He Qing He Qing He Qing He Yingxuan Yin Yingxuan Yin Yingxuan Yin Yingxuan Yin Yinjuan Wu Yinjuan Wu Yinjuan Wu Yinjuan Wu Xuerong Li Xuerong Li Xuerong Li Xuerong Li |
| author_facet |
Caiqin Wang Caiqin Wang Caiqin Wang Caiqin Wang Caiqin Wang Qing He Qing He Qing He Qing He Yingxuan Yin Yingxuan Yin Yingxuan Yin Yingxuan Yin Yinjuan Wu Yinjuan Wu Yinjuan Wu Yinjuan Wu Xuerong Li Xuerong Li Xuerong Li Xuerong Li |
| author_sort |
Caiqin Wang |
| title |
Clonorchis sinensis Granulin Promotes Malignant Transformation of Hepatocyte Through EGFR-Mediated RAS/MAPK/ERK and PI3K/Akt Signaling Pathways |
| title_short |
Clonorchis sinensis Granulin Promotes Malignant Transformation of Hepatocyte Through EGFR-Mediated RAS/MAPK/ERK and PI3K/Akt Signaling Pathways |
| title_full |
Clonorchis sinensis Granulin Promotes Malignant Transformation of Hepatocyte Through EGFR-Mediated RAS/MAPK/ERK and PI3K/Akt Signaling Pathways |
| title_fullStr |
Clonorchis sinensis Granulin Promotes Malignant Transformation of Hepatocyte Through EGFR-Mediated RAS/MAPK/ERK and PI3K/Akt Signaling Pathways |
| title_full_unstemmed |
Clonorchis sinensis Granulin Promotes Malignant Transformation of Hepatocyte Through EGFR-Mediated RAS/MAPK/ERK and PI3K/Akt Signaling Pathways |
| title_sort |
clonorchis sinensis granulin promotes malignant transformation of hepatocyte through egfr-mediated ras/mapk/erk and pi3k/akt signaling pathways |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/782eb554ac32426b83386b955d631693 |
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