PD173074 blocks G1/S transition via CUL3-mediated ubiquitin protease in HepG2 and Hep3B cells.
Fibroblast growth factor receptors (FGFRs) are frequently altered in a variety of human cancer cells and are overexpressed in hepatocellular carcinoma (HCC). Several literatures have proven that they are efficacious for HCC therapy, however, the underlying mechanism remains unclear. Here, we found F...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0234708 |
| _version_ | 1819125516628656128 |
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| author | Chuchu Qiao Hongyan Qian Jue Wang Tingting Zhao Pengyu Ma Sicen Wang Tao Zhang Xinshe Liu |
| author_facet | Chuchu Qiao Hongyan Qian Jue Wang Tingting Zhao Pengyu Ma Sicen Wang Tao Zhang Xinshe Liu |
| author_sort | Chuchu Qiao |
| collection | DOAJ |
| description | Fibroblast growth factor receptors (FGFRs) are frequently altered in a variety of human cancer cells and are overexpressed in hepatocellular carcinoma (HCC). Several literatures have proven that they are efficacious for HCC therapy, however, the underlying mechanism remains unclear. Here, we found FGFR4 was overexpressed in HCC cell lines HepG2 and Hep3B and we used PD173074, an FGFR4 inhibitor, to explore the role of FGFR4 and its underlying mechanism in these cell lines. The results showed that PD173074 significantly arrested HepG2 and Hep3B cells in G1 phase and inhibited cell proliferation. Furthermore, Western blot analysis revealed that PD173074 decreased the levels of P-FRS2α, P-ERK, CDK2, cyclin E and NF-κB (p65) in the nucleus while it increased the levels of ubiquitin and CUL3, an E3 ubiquitin ligase which involves in cyclin E degradation. Meanwhile, the data from RT-qPCR showed that PD173074 also decreased miR-141 level. In conclusion, these results suggest that FGFR4 is involved in HCC by ERK/CUL3/cyclin E signaling pathway, and the finding may provide a potential theoretical basis for treatment by targeting FGFR4 in HCC. |
| first_indexed | 2024-12-22T07:41:23Z |
| format | Article |
| id | doaj.art-749e8f629f4f4b398d147fa898759eff |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T07:41:23Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-749e8f629f4f4b398d147fa898759eff2022-12-21T18:33:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01156e023470810.1371/journal.pone.0234708PD173074 blocks G1/S transition via CUL3-mediated ubiquitin protease in HepG2 and Hep3B cells.Chuchu QiaoHongyan QianJue WangTingting ZhaoPengyu MaSicen WangTao ZhangXinshe LiuFibroblast growth factor receptors (FGFRs) are frequently altered in a variety of human cancer cells and are overexpressed in hepatocellular carcinoma (HCC). Several literatures have proven that they are efficacious for HCC therapy, however, the underlying mechanism remains unclear. Here, we found FGFR4 was overexpressed in HCC cell lines HepG2 and Hep3B and we used PD173074, an FGFR4 inhibitor, to explore the role of FGFR4 and its underlying mechanism in these cell lines. The results showed that PD173074 significantly arrested HepG2 and Hep3B cells in G1 phase and inhibited cell proliferation. Furthermore, Western blot analysis revealed that PD173074 decreased the levels of P-FRS2α, P-ERK, CDK2, cyclin E and NF-κB (p65) in the nucleus while it increased the levels of ubiquitin and CUL3, an E3 ubiquitin ligase which involves in cyclin E degradation. Meanwhile, the data from RT-qPCR showed that PD173074 also decreased miR-141 level. In conclusion, these results suggest that FGFR4 is involved in HCC by ERK/CUL3/cyclin E signaling pathway, and the finding may provide a potential theoretical basis for treatment by targeting FGFR4 in HCC.https://doi.org/10.1371/journal.pone.0234708 |
| spellingShingle | Chuchu Qiao Hongyan Qian Jue Wang Tingting Zhao Pengyu Ma Sicen Wang Tao Zhang Xinshe Liu PD173074 blocks G1/S transition via CUL3-mediated ubiquitin protease in HepG2 and Hep3B cells. PLoS ONE |
| title | PD173074 blocks G1/S transition via CUL3-mediated ubiquitin protease in HepG2 and Hep3B cells. |
| title_full | PD173074 blocks G1/S transition via CUL3-mediated ubiquitin protease in HepG2 and Hep3B cells. |
| title_fullStr | PD173074 blocks G1/S transition via CUL3-mediated ubiquitin protease in HepG2 and Hep3B cells. |
| title_full_unstemmed | PD173074 blocks G1/S transition via CUL3-mediated ubiquitin protease in HepG2 and Hep3B cells. |
| title_short | PD173074 blocks G1/S transition via CUL3-mediated ubiquitin protease in HepG2 and Hep3B cells. |
| title_sort | pd173074 blocks g1 s transition via cul3 mediated ubiquitin protease in hepg2 and hep3b cells |
| url | https://doi.org/10.1371/journal.pone.0234708 |
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