RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation
Lung cancer is the leading cause of cancer death worldwide, and the overall survival rate of advanced lung cancer patients is unsatisfactory. Ribosomal proteins (RPs) play important roles in carcinogenesis. However, the role of RPL32 in lung cancer has not been demonstrated. Here, we report that RPL...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253120301451 |
| _version_ | 1818212068417863680 |
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| author | Jiansheng Xie Wei Zhang Xiaojing Liang Chong Shuai Yubin Zhou Hongming Pan Yunhai Yang Weidong Han |
| author_facet | Jiansheng Xie Wei Zhang Xiaojing Liang Chong Shuai Yubin Zhou Hongming Pan Yunhai Yang Weidong Han |
| author_sort | Jiansheng Xie |
| collection | DOAJ |
| description | Lung cancer is the leading cause of cancer death worldwide, and the overall survival rate of advanced lung cancer patients is unsatisfactory. Ribosomal proteins (RPs) play important roles in carcinogenesis. However, the role of RPL32 in lung cancer has not been demonstrated. Here, we report that RPL32 is aberrantly, highly expressed in lung cancer tissues and that the overexpression of RPL32 is correlated with the poor prognosis of these patients. RPL32 silencing significantly inhibited the proliferation of lung cancer cells, with an observed p53 accumulation and cell-cycle arrest. Mechanistically, knockdown of RPL32 resulted in ribosomal stress and affected rRNA maturation. RPL5 and RPL11 sensed stress and translocated from the nucleus to the nucleoplasm, where they bound to murine double minute 2 (MDM2), an important p53 E3 ubiquitin ligase, which resulted in p53 accumulation and inhibition of cancer cell proliferation. As lung cancer cells usually express high levels of Toll-like receptor 9 (TLR9), we conjugated RPL32 small interfering RNA (siRNA) to the TLR9 ligand CpG to generate CpG-RPL32 siRNA, which could stabilize and guide RPL32 siRNA to lung cancer cells. Excitingly, CpG-RPL32 siRNA displayed strong anticancer abilities in lung cancer xenografts. Therefore, RPL32 is expected to be a potential target for lung cancer treatment. |
| first_indexed | 2024-12-12T05:42:31Z |
| format | Article |
| id | doaj.art-6a4fb5848bc444fbb2bd87d6b353a22f |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-12T05:42:31Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-6a4fb5848bc444fbb2bd87d6b353a22f2022-12-22T00:35:52ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-09-01217585RPL32 Promotes Lung Cancer Progression by Facilitating p53 DegradationJiansheng Xie0Wei Zhang1Xiaojing Liang2Chong Shuai3Yubin Zhou4Hongming Pan5Yunhai Yang6Weidong Han7Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Laboratory of Cancer Biology, Institute of Clinical Science, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Laboratory of Cancer Biology, Institute of Clinical Science, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaCenter for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030, USADepartment of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Laboratory of Cancer Biology, Institute of Clinical Science, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Corresponding author: Hongming Pan, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3# East Qinchun Road, Hangzhou, Zhejiang 310016, China.Cancer Center of Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China; Corresponding author: Yunhai Yang, Cancer Center of Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 200030, China.Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Laboratory of Cancer Biology, Institute of Clinical Science, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Corresponding author: Weidong Han, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3# East Qinchun Road, Hangzhou, Zhejiang 310016, China.Lung cancer is the leading cause of cancer death worldwide, and the overall survival rate of advanced lung cancer patients is unsatisfactory. Ribosomal proteins (RPs) play important roles in carcinogenesis. However, the role of RPL32 in lung cancer has not been demonstrated. Here, we report that RPL32 is aberrantly, highly expressed in lung cancer tissues and that the overexpression of RPL32 is correlated with the poor prognosis of these patients. RPL32 silencing significantly inhibited the proliferation of lung cancer cells, with an observed p53 accumulation and cell-cycle arrest. Mechanistically, knockdown of RPL32 resulted in ribosomal stress and affected rRNA maturation. RPL5 and RPL11 sensed stress and translocated from the nucleus to the nucleoplasm, where they bound to murine double minute 2 (MDM2), an important p53 E3 ubiquitin ligase, which resulted in p53 accumulation and inhibition of cancer cell proliferation. As lung cancer cells usually express high levels of Toll-like receptor 9 (TLR9), we conjugated RPL32 small interfering RNA (siRNA) to the TLR9 ligand CpG to generate CpG-RPL32 siRNA, which could stabilize and guide RPL32 siRNA to lung cancer cells. Excitingly, CpG-RPL32 siRNA displayed strong anticancer abilities in lung cancer xenografts. Therefore, RPL32 is expected to be a potential target for lung cancer treatment.http://www.sciencedirect.com/science/article/pii/S2162253120301451lung cancerRPL32p53ribosomal stress |
| spellingShingle | Jiansheng Xie Wei Zhang Xiaojing Liang Chong Shuai Yubin Zhou Hongming Pan Yunhai Yang Weidong Han RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation Molecular Therapy: Nucleic Acids lung cancer RPL32 p53 ribosomal stress |
| title | RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation |
| title_full | RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation |
| title_fullStr | RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation |
| title_full_unstemmed | RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation |
| title_short | RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation |
| title_sort | rpl32 promotes lung cancer progression by facilitating p53 degradation |
| topic | lung cancer RPL32 p53 ribosomal stress |
| url | http://www.sciencedirect.com/science/article/pii/S2162253120301451 |
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