RRP15 deficiency induces ribosome stress to inhibit colorectal cancer proliferation and metastasis via LZTS2-mediated β-catenin suppression
Abstract Ribosome biogenesis (RiBi) plays a pivotal role in carcinogenesis by regulating protein translation and stress response. Here, we find that RRP15, a nucleolar protein critical for RiBi and checkpoint control, is frequently upregulated in primary CRCs and higher RRP15 expression positively c...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-02-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-05578-6 |
| _version_ | 1828034958017429504 |
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| author | Zhixiong Dong Jinhai Li Wenqing Dai Dongbo Yu Youjuan Zhao Shuanghui Liu Xuanwen Li Zhengzheng Zhang Rui Zhang Xue Liang Qingran Kong Shengnan Jin Hao Jiang Wei Jiang Chunming Ding |
| author_facet | Zhixiong Dong Jinhai Li Wenqing Dai Dongbo Yu Youjuan Zhao Shuanghui Liu Xuanwen Li Zhengzheng Zhang Rui Zhang Xue Liang Qingran Kong Shengnan Jin Hao Jiang Wei Jiang Chunming Ding |
| author_sort | Zhixiong Dong |
| collection | DOAJ |
| description | Abstract Ribosome biogenesis (RiBi) plays a pivotal role in carcinogenesis by regulating protein translation and stress response. Here, we find that RRP15, a nucleolar protein critical for RiBi and checkpoint control, is frequently upregulated in primary CRCs and higher RRP15 expression positively correlated with TNM stage (P < 0.0001) and poor survival of CRC patients (P = 0.0011). Functionally, silencing RRP15 induces ribosome stress, cell cycle arrest, and apoptosis, resulting in suppression of cell proliferation and metastasis. Overexpression of RRP15 promotes cell proliferation and metastasis. Mechanistically, ribosome stress induced by RRP15 deficiency facilitates translation of TOP mRNA LZTS2 (Leucine zipper tumor suppressor 2), leading to the nuclear export and degradation of β-catenin to suppress Wnt/β-catenin signaling in CRC. In conclusion, ribosome stress induced by RRP15 deficiency inhibits CRC cell proliferation and metastasis via suppressing the Wnt/β-catenin pathway, suggesting a potential new target in high-RiBi CRC patients. |
| first_indexed | 2024-04-10T15:40:47Z |
| format | Article |
| id | doaj.art-42528bb3297e49eda7cc8158268d8da6 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-10T15:40:47Z |
| publishDate | 2023-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-42528bb3297e49eda7cc8158268d8da62023-02-12T12:24:13ZengNature Publishing GroupCell Death and Disease2041-48892023-02-0114211510.1038/s41419-023-05578-6RRP15 deficiency induces ribosome stress to inhibit colorectal cancer proliferation and metastasis via LZTS2-mediated β-catenin suppressionZhixiong Dong0Jinhai Li1Wenqing Dai2Dongbo Yu3Youjuan Zhao4Shuanghui Liu5Xuanwen Li6Zhengzheng Zhang7Rui Zhang8Xue Liang9Qingran Kong10Shengnan Jin11Hao Jiang12Wei Jiang13Chunming Ding14Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Science, Wenzhou Medical UniversityDepartment of Liver and Gall Surgery, the Third Affiliated Hospital of Wenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Science, Wenzhou Medical UniversityState Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeZhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Science, Wenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Science, Wenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Science, Wenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Science, Wenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Science, Wenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Science, Wenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Science, Wenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Science, Wenzhou Medical UniversityDepartment of Biomedical Informatics, School of Life Sciences, Central South UniversityState Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeZhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Science, Wenzhou Medical UniversityAbstract Ribosome biogenesis (RiBi) plays a pivotal role in carcinogenesis by regulating protein translation and stress response. Here, we find that RRP15, a nucleolar protein critical for RiBi and checkpoint control, is frequently upregulated in primary CRCs and higher RRP15 expression positively correlated with TNM stage (P < 0.0001) and poor survival of CRC patients (P = 0.0011). Functionally, silencing RRP15 induces ribosome stress, cell cycle arrest, and apoptosis, resulting in suppression of cell proliferation and metastasis. Overexpression of RRP15 promotes cell proliferation and metastasis. Mechanistically, ribosome stress induced by RRP15 deficiency facilitates translation of TOP mRNA LZTS2 (Leucine zipper tumor suppressor 2), leading to the nuclear export and degradation of β-catenin to suppress Wnt/β-catenin signaling in CRC. In conclusion, ribosome stress induced by RRP15 deficiency inhibits CRC cell proliferation and metastasis via suppressing the Wnt/β-catenin pathway, suggesting a potential new target in high-RiBi CRC patients.https://doi.org/10.1038/s41419-023-05578-6 |
| spellingShingle | Zhixiong Dong Jinhai Li Wenqing Dai Dongbo Yu Youjuan Zhao Shuanghui Liu Xuanwen Li Zhengzheng Zhang Rui Zhang Xue Liang Qingran Kong Shengnan Jin Hao Jiang Wei Jiang Chunming Ding RRP15 deficiency induces ribosome stress to inhibit colorectal cancer proliferation and metastasis via LZTS2-mediated β-catenin suppression Cell Death and Disease |
| title | RRP15 deficiency induces ribosome stress to inhibit colorectal cancer proliferation and metastasis via LZTS2-mediated β-catenin suppression |
| title_full | RRP15 deficiency induces ribosome stress to inhibit colorectal cancer proliferation and metastasis via LZTS2-mediated β-catenin suppression |
| title_fullStr | RRP15 deficiency induces ribosome stress to inhibit colorectal cancer proliferation and metastasis via LZTS2-mediated β-catenin suppression |
| title_full_unstemmed | RRP15 deficiency induces ribosome stress to inhibit colorectal cancer proliferation and metastasis via LZTS2-mediated β-catenin suppression |
| title_short | RRP15 deficiency induces ribosome stress to inhibit colorectal cancer proliferation and metastasis via LZTS2-mediated β-catenin suppression |
| title_sort | rrp15 deficiency induces ribosome stress to inhibit colorectal cancer proliferation and metastasis via lzts2 mediated β catenin suppression |
| url | https://doi.org/10.1038/s41419-023-05578-6 |
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