RPL15 promotes hepatocellular carcinoma progression via regulation of RPs-MDM2-p53 signaling pathway
Abstract Backround RPL15 has been found to participate in human tumorigenesis. However, its function and regulatory mechanism in hepatocellular carcinoma (HCC) development are still unclear. Current study investigated the effects of RPL15 in HCC. Methods The expression of RPL15 in clinical tissues a...
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-022-02555-5 |
| _version_ | 1818022182430703616 |
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| author | Rui Shi Zirong Liu |
| author_facet | Rui Shi Zirong Liu |
| author_sort | Rui Shi |
| collection | DOAJ |
| description | Abstract Backround RPL15 has been found to participate in human tumorigenesis. However, its function and regulatory mechanism in hepatocellular carcinoma (HCC) development are still unclear. Current study investigated the effects of RPL15 in HCC. Methods The expression of RPL15 in clinical tissues and cell lines of HCC was detected by RT-qPCR, Western blotting, and Immunohistochemistry (IHC). Colony formation, CCK-8, flow cytometry, Wound healing and Transwell invasion assays, were used to detect the carcinoma progression of HCC cells with RPL15 overexpression or knockdown in vitro. A xenograft model was constructed to assess the effect of RPL15 knockdown on HCC cells in vivo. The expression of CDK2 and Cyclin E1 related to cell cycles, Bax and Bcl-2 related to cell apoptosis, E-cadherin, N-cadherin and Vimentin related to epithelial–mesenchymal transition (EMT), p53 and p21 related to p53 signaling pathway, were detected by Western blotting. The connection between p53, MDM2 and RPL5/11 affected by RPL15 was analyzed using immunoprecipitation and Cycloheximide (CHX) chase assay. Results Elevated RPL15 was identified in HCC tissues, which was not only a prediction for the poor prognosis of HCC patients, but also associated with the malignant progression of HCC. RPL15 silencing arrested HCC cell cycle, suppressed HCC cell colony formation, proliferation, invasion, and migration, and induce cell apoptosis. On the contrary, RPL15 upregulation exerted opposite effects. Results also indicated that HCC cell invasion and migration were associated with EMT, and that the RPs-MDM2-p53 pathway was implicated in RPL15-mediated oncogenic transformation. In addition, RPL15 knockdown significantly suppressed HCC xenografts growth. Conclusions RPL15 played crucial roles in HCC progression and metastasis, serving as a promising candidate for targeted therapies. |
| first_indexed | 2024-04-14T08:28:03Z |
| format | Article |
| id | doaj.art-6db7344eb6c74f029116734a804a7ed3 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-04-14T08:28:03Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-6db7344eb6c74f029116734a804a7ed32022-12-22T02:03:59ZengBMCCancer Cell International1475-28672022-04-0122111310.1186/s12935-022-02555-5RPL15 promotes hepatocellular carcinoma progression via regulation of RPs-MDM2-p53 signaling pathwayRui Shi0Zirong Liu1Department of Hepatobiliary Surgery, Tianjin First Central HospitalDepartment of Hepatobiliary Surgery, Tianjin First Central HospitalAbstract Backround RPL15 has been found to participate in human tumorigenesis. However, its function and regulatory mechanism in hepatocellular carcinoma (HCC) development are still unclear. Current study investigated the effects of RPL15 in HCC. Methods The expression of RPL15 in clinical tissues and cell lines of HCC was detected by RT-qPCR, Western blotting, and Immunohistochemistry (IHC). Colony formation, CCK-8, flow cytometry, Wound healing and Transwell invasion assays, were used to detect the carcinoma progression of HCC cells with RPL15 overexpression or knockdown in vitro. A xenograft model was constructed to assess the effect of RPL15 knockdown on HCC cells in vivo. The expression of CDK2 and Cyclin E1 related to cell cycles, Bax and Bcl-2 related to cell apoptosis, E-cadherin, N-cadherin and Vimentin related to epithelial–mesenchymal transition (EMT), p53 and p21 related to p53 signaling pathway, were detected by Western blotting. The connection between p53, MDM2 and RPL5/11 affected by RPL15 was analyzed using immunoprecipitation and Cycloheximide (CHX) chase assay. Results Elevated RPL15 was identified in HCC tissues, which was not only a prediction for the poor prognosis of HCC patients, but also associated with the malignant progression of HCC. RPL15 silencing arrested HCC cell cycle, suppressed HCC cell colony formation, proliferation, invasion, and migration, and induce cell apoptosis. On the contrary, RPL15 upregulation exerted opposite effects. Results also indicated that HCC cell invasion and migration were associated with EMT, and that the RPs-MDM2-p53 pathway was implicated in RPL15-mediated oncogenic transformation. In addition, RPL15 knockdown significantly suppressed HCC xenografts growth. Conclusions RPL15 played crucial roles in HCC progression and metastasis, serving as a promising candidate for targeted therapies.https://doi.org/10.1186/s12935-022-02555-5Hepatocellular carcinomaMDM2p53RPL15Tumor progression |
| spellingShingle | Rui Shi Zirong Liu RPL15 promotes hepatocellular carcinoma progression via regulation of RPs-MDM2-p53 signaling pathway Cancer Cell International Hepatocellular carcinoma MDM2 p53 RPL15 Tumor progression |
| title | RPL15 promotes hepatocellular carcinoma progression via regulation of RPs-MDM2-p53 signaling pathway |
| title_full | RPL15 promotes hepatocellular carcinoma progression via regulation of RPs-MDM2-p53 signaling pathway |
| title_fullStr | RPL15 promotes hepatocellular carcinoma progression via regulation of RPs-MDM2-p53 signaling pathway |
| title_full_unstemmed | RPL15 promotes hepatocellular carcinoma progression via regulation of RPs-MDM2-p53 signaling pathway |
| title_short | RPL15 promotes hepatocellular carcinoma progression via regulation of RPs-MDM2-p53 signaling pathway |
| title_sort | rpl15 promotes hepatocellular carcinoma progression via regulation of rps mdm2 p53 signaling pathway |
| topic | Hepatocellular carcinoma MDM2 p53 RPL15 Tumor progression |
| url | https://doi.org/10.1186/s12935-022-02555-5 |
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