CircRNA circ_0124554 blocked the ubiquitination of AKT promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancer
Abstract Colorectal cancer (CRC) is the fourth most common cancer in men and the third most common cancer in women worldwide. The incidence and mortality of CRC was increasing rapidly in China. Lymph node-negative colorectal cancer patients with synchronous liver metastasis (LNLM1) was defined as “s...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-03-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-03565-3 |
| _version_ | 1818734862935261184 |
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| author | Junwei Tang Chuan Zhang Yuanjian Huang Lu Wang Ziwei Xu Dongsheng Zhang Yue Zhang Wen Peng Yifei Feng Yueming Sun |
| author_facet | Junwei Tang Chuan Zhang Yuanjian Huang Lu Wang Ziwei Xu Dongsheng Zhang Yue Zhang Wen Peng Yifei Feng Yueming Sun |
| author_sort | Junwei Tang |
| collection | DOAJ |
| description | Abstract Colorectal cancer (CRC) is the fourth most common cancer in men and the third most common cancer in women worldwide. The incidence and mortality of CRC was increasing rapidly in China. Lymph node-negative colorectal cancer patients with synchronous liver metastasis (LNLM1) was defined as “skip” lymph vascular invasion on hepatic metastasis, who presenting poor prognosis. We aiming to investigate the potential mechanism for the “skip” lymph vascular invasion on hepatic metastasis in colorectal cancer. The microarray was applied for screening the transcription landscape of circRNA in lymph node negative CRC patients with synchronous liver metastasis (LNLM1) or without liver metastasis (LNLM0). We identified the aberrant increased circRNA circ_0124554 (also entitled as circ-LNLM) in tumor tissues of LNLM1 patients comparing with either the tumor tissues of LNLM0 or adjacent tissues of LNLM1. Circ-LNLM1 expression was highly correlated with liver metastasis and vascular invasion. Ectopic expression of cytoplasmic located circ-LNLM could promote invasion of CRC cells and induced the liver metastasis in animal models through the direct binding with AKT. The phosphorylation of AKT (T308/S473) was activated due to the blocked ubiquitination site of Lys in 0-52aa peptide of circ-LNLM. Endogenous plasma expression of circ-LNLM induced poor prognosis of LNLM1 and could distinguish LNLM1 patients from LNLM0. In conclusion, the circ-LNLM blocked the ubiquitination of AKT could promote the early metastasis especially for the lymph node-negative colorectal cancer patients with synchronous liver metastasis. The circ-LNLM might be prognosis and diagnosis biomarker for LNLM1 patients. |
| first_indexed | 2024-12-18T00:12:07Z |
| format | Article |
| id | doaj.art-9fd8cbee08ec4fe5905b1cd7c5a66657 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-18T00:12:07Z |
| publishDate | 2021-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-9fd8cbee08ec4fe5905b1cd7c5a666572022-12-21T21:27:39ZengNature Publishing GroupCell Death and Disease2041-48892021-03-0112311210.1038/s41419-021-03565-3CircRNA circ_0124554 blocked the ubiquitination of AKT promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancerJunwei Tang0Chuan Zhang1Yuanjian Huang2Lu Wang3Ziwei Xu4Dongsheng Zhang5Yue Zhang6Wen Peng7Yifei Feng8Yueming Sun9Colorectal Surgery Division, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityColorectal Surgery Division, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityColorectal Surgery Division, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityColorectal Surgery Division, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityColorectal Surgery Division, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityColorectal Surgery Division, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityColorectal Surgery Division, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityColorectal Surgery Division, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityColorectal Surgery Division, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityColorectal Surgery Division, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityAbstract Colorectal cancer (CRC) is the fourth most common cancer in men and the third most common cancer in women worldwide. The incidence and mortality of CRC was increasing rapidly in China. Lymph node-negative colorectal cancer patients with synchronous liver metastasis (LNLM1) was defined as “skip” lymph vascular invasion on hepatic metastasis, who presenting poor prognosis. We aiming to investigate the potential mechanism for the “skip” lymph vascular invasion on hepatic metastasis in colorectal cancer. The microarray was applied for screening the transcription landscape of circRNA in lymph node negative CRC patients with synchronous liver metastasis (LNLM1) or without liver metastasis (LNLM0). We identified the aberrant increased circRNA circ_0124554 (also entitled as circ-LNLM) in tumor tissues of LNLM1 patients comparing with either the tumor tissues of LNLM0 or adjacent tissues of LNLM1. Circ-LNLM1 expression was highly correlated with liver metastasis and vascular invasion. Ectopic expression of cytoplasmic located circ-LNLM could promote invasion of CRC cells and induced the liver metastasis in animal models through the direct binding with AKT. The phosphorylation of AKT (T308/S473) was activated due to the blocked ubiquitination site of Lys in 0-52aa peptide of circ-LNLM. Endogenous plasma expression of circ-LNLM induced poor prognosis of LNLM1 and could distinguish LNLM1 patients from LNLM0. In conclusion, the circ-LNLM blocked the ubiquitination of AKT could promote the early metastasis especially for the lymph node-negative colorectal cancer patients with synchronous liver metastasis. The circ-LNLM might be prognosis and diagnosis biomarker for LNLM1 patients.https://doi.org/10.1038/s41419-021-03565-3 |
| spellingShingle | Junwei Tang Chuan Zhang Yuanjian Huang Lu Wang Ziwei Xu Dongsheng Zhang Yue Zhang Wen Peng Yifei Feng Yueming Sun CircRNA circ_0124554 blocked the ubiquitination of AKT promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancer Cell Death and Disease |
| title | CircRNA circ_0124554 blocked the ubiquitination of AKT promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancer |
| title_full | CircRNA circ_0124554 blocked the ubiquitination of AKT promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancer |
| title_fullStr | CircRNA circ_0124554 blocked the ubiquitination of AKT promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancer |
| title_full_unstemmed | CircRNA circ_0124554 blocked the ubiquitination of AKT promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancer |
| title_short | CircRNA circ_0124554 blocked the ubiquitination of AKT promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancer |
| title_sort | circrna circ 0124554 blocked the ubiquitination of akt promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancer |
| url | https://doi.org/10.1038/s41419-021-03565-3 |
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