N6-methyladenosine modification of circ_0003215 suppresses the pentose phosphate pathway and malignancy of colorectal cancer through the miR-663b/DLG4/G6PD axis
Abstract Circular RNAs (circRNAs) are a recently discovered kind of regulatory RNAs that have emerged as critical biomarkers of various types of cancers. Metabolic reprogramming has gradually been identified as a distinct hallmark of cancer cells. The pentose phosphate pathway (PPP) plays an indispe...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-09-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05245-2 |
| _version_ | 1828175474571870208 |
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| author | Baoxiang Chen Yuntian Hong Rui Gui Huabin Zheng Shunhua Tian Xiang Zhai Xiaoyu Xie Quanjiao Chen Qun Qian Xianghai Ren Lifang Fan Congqing Jiang |
| author_facet | Baoxiang Chen Yuntian Hong Rui Gui Huabin Zheng Shunhua Tian Xiang Zhai Xiaoyu Xie Quanjiao Chen Qun Qian Xianghai Ren Lifang Fan Congqing Jiang |
| author_sort | Baoxiang Chen |
| collection | DOAJ |
| description | Abstract Circular RNAs (circRNAs) are a recently discovered kind of regulatory RNAs that have emerged as critical biomarkers of various types of cancers. Metabolic reprogramming has gradually been identified as a distinct hallmark of cancer cells. The pentose phosphate pathway (PPP) plays an indispensable role in satisfying the bioenergetic and biosynthetic demands of cancer cells. However, little is known about the role of circRNAs and PPP in colorectal cancer (CRC). The novel circ_0003215 was identified at low levels in CRC and was negatively correlated with larger tumor size, higher TNM stage, and lymph node metastasis. The decreased level of circ_0003215 was resulted from the RNA degradation by m6A writer protein YTHDF2. A series of functional assays demonstrated that circ_0003215 inhibited cell proliferation, migration, invasion, and CRC tumor metastasis in vivo and in vitro. Moreover, circ_0003215 regulated the expression of DLG4 via sponging miR-663b, thereby inducing the metabolic reprogramming in CRC. Mechanismly, DLG4 inhibited the PPP through the K48-linked ubiquitination of glucose-6-phosphate dehydrogenase (G6PD). Taken together, we have identified m6A-modified circ_0003215 as a novel regulator of metabolic glucose reprogramming that inhibited the PPP and the malignant phenotype of CRC via the miR-663b/DLG4/G6PD axis. |
| first_indexed | 2024-04-12T04:28:38Z |
| format | Article |
| id | doaj.art-25466033aeb14f5e960cb498db580393 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-12T04:28:38Z |
| publishDate | 2022-09-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-25466033aeb14f5e960cb498db5803932022-12-22T03:48:00ZengNature Publishing GroupCell Death and Disease2041-48892022-09-0113911610.1038/s41419-022-05245-2N6-methyladenosine modification of circ_0003215 suppresses the pentose phosphate pathway and malignancy of colorectal cancer through the miR-663b/DLG4/G6PD axisBaoxiang Chen0Yuntian Hong1Rui Gui2Huabin Zheng3Shunhua Tian4Xiang Zhai5Xiaoyu Xie6Quanjiao Chen7Qun Qian8Xianghai Ren9Lifang Fan10Congqing Jiang11Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University)CAS Key Laboratory of Special Pathogens and Biosafety, CAS Center for Influenza Research and Early Warning, Wuhan Institute of Virology, Chinese Academy of SciencesDepartment of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan UniversityCAS Key Laboratory of Special Pathogens and Biosafety, CAS Center for Influenza Research and Early Warning, Wuhan Institute of Virology, Chinese Academy of SciencesDepartment of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Pathology, Zhongnan Hospital of Wuhan UniversityDepartment of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan UniversityAbstract Circular RNAs (circRNAs) are a recently discovered kind of regulatory RNAs that have emerged as critical biomarkers of various types of cancers. Metabolic reprogramming has gradually been identified as a distinct hallmark of cancer cells. The pentose phosphate pathway (PPP) plays an indispensable role in satisfying the bioenergetic and biosynthetic demands of cancer cells. However, little is known about the role of circRNAs and PPP in colorectal cancer (CRC). The novel circ_0003215 was identified at low levels in CRC and was negatively correlated with larger tumor size, higher TNM stage, and lymph node metastasis. The decreased level of circ_0003215 was resulted from the RNA degradation by m6A writer protein YTHDF2. A series of functional assays demonstrated that circ_0003215 inhibited cell proliferation, migration, invasion, and CRC tumor metastasis in vivo and in vitro. Moreover, circ_0003215 regulated the expression of DLG4 via sponging miR-663b, thereby inducing the metabolic reprogramming in CRC. Mechanismly, DLG4 inhibited the PPP through the K48-linked ubiquitination of glucose-6-phosphate dehydrogenase (G6PD). Taken together, we have identified m6A-modified circ_0003215 as a novel regulator of metabolic glucose reprogramming that inhibited the PPP and the malignant phenotype of CRC via the miR-663b/DLG4/G6PD axis.https://doi.org/10.1038/s41419-022-05245-2 |
| spellingShingle | Baoxiang Chen Yuntian Hong Rui Gui Huabin Zheng Shunhua Tian Xiang Zhai Xiaoyu Xie Quanjiao Chen Qun Qian Xianghai Ren Lifang Fan Congqing Jiang N6-methyladenosine modification of circ_0003215 suppresses the pentose phosphate pathway and malignancy of colorectal cancer through the miR-663b/DLG4/G6PD axis Cell Death and Disease |
| title | N6-methyladenosine modification of circ_0003215 suppresses the pentose phosphate pathway and malignancy of colorectal cancer through the miR-663b/DLG4/G6PD axis |
| title_full | N6-methyladenosine modification of circ_0003215 suppresses the pentose phosphate pathway and malignancy of colorectal cancer through the miR-663b/DLG4/G6PD axis |
| title_fullStr | N6-methyladenosine modification of circ_0003215 suppresses the pentose phosphate pathway and malignancy of colorectal cancer through the miR-663b/DLG4/G6PD axis |
| title_full_unstemmed | N6-methyladenosine modification of circ_0003215 suppresses the pentose phosphate pathway and malignancy of colorectal cancer through the miR-663b/DLG4/G6PD axis |
| title_short | N6-methyladenosine modification of circ_0003215 suppresses the pentose phosphate pathway and malignancy of colorectal cancer through the miR-663b/DLG4/G6PD axis |
| title_sort | n6 methyladenosine modification of circ 0003215 suppresses the pentose phosphate pathway and malignancy of colorectal cancer through the mir 663b dlg4 g6pd axis |
| url | https://doi.org/10.1038/s41419-022-05245-2 |
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