The m<sup>7</sup>G Reader NCBP2 Promotes Pancreatic Cancer Progression by Upregulating MAPK/ERK Signaling
PDAC is one of the most common malignant tumors worldwide. The difficulty of early diagnosis and lack of effective treatment are the main reasons for its poor prognosis. Therefore, it is urgent to identify novel diagnostic and therapeutic targets for PDAC patients. The m<sup>7</sup>G met...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/22/5454 |
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| author | Jiancong Xie Taiwei Mo Ruibing Li Hao Zhang Guanzhan Liang Tao Ma Jing Chen Hanlin Xie Xiaofeng Wen Tuo Hu Zhenyu Xian Weidong Pan |
| author_facet | Jiancong Xie Taiwei Mo Ruibing Li Hao Zhang Guanzhan Liang Tao Ma Jing Chen Hanlin Xie Xiaofeng Wen Tuo Hu Zhenyu Xian Weidong Pan |
| author_sort | Jiancong Xie |
| collection | DOAJ |
| description | PDAC is one of the most common malignant tumors worldwide. The difficulty of early diagnosis and lack of effective treatment are the main reasons for its poor prognosis. Therefore, it is urgent to identify novel diagnostic and therapeutic targets for PDAC patients. The m<sup>7</sup>G methylation is a common type of RNA modification that plays a pivotal role in regulating tumor development. However, the correlation between m<sup>7</sup>G regulatory genes and PDAC progression remains unclear. By integrating gene expression and related clinical information of PDAC patients from TCGA and GEO cohorts, m<sup>7</sup>G binding protein NCBP2 was found to be highly expressed in PDAC patients. More importantly, PDAC patients with high NCBP2 expression had a worse prognosis. Stable NCBP2-knockdown and overexpression PDAC cell lines were constructed to further perform in-vitro and in-vivo experiments. NCBP2-knockdown significantly inhibited PDAC cell proliferation, while overexpression of NCBP2 dramatically promoted PDAC cell growth. Mechanistically, NCBP2 enhanced the translation of c-JUN, which in turn activated MEK/ERK signaling to promote PDAC progression. In conclusion, our study reveals that m<sup>7</sup>G reader NCBP2 promotes PDAC progression by activating MEK/ERK pathway, which could serve as a novel therapeutic target for PDAC patients. |
| first_indexed | 2024-03-09T16:56:40Z |
| format | Article |
| id | doaj.art-60261288ea3042c8bc9309a81e5f047e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T16:56:40Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-60261288ea3042c8bc9309a81e5f047e2023-11-24T14:34:34ZengMDPI AGCancers2072-66942023-11-011522545410.3390/cancers15225454The m<sup>7</sup>G Reader NCBP2 Promotes Pancreatic Cancer Progression by Upregulating MAPK/ERK SignalingJiancong Xie0Taiwei Mo1Ruibing Li2Hao Zhang3Guanzhan Liang4Tao Ma5Jing Chen6Hanlin Xie7Xiaofeng Wen8Tuo Hu9Zhenyu Xian10Weidong Pan11Department of General Surgery (Pancreatic Hepatobiliary Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, ChinaDepartment of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510630, ChinaDepartment of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, ChinaDepartment of General Surgery (Pancreatic Hepatobiliary Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, ChinaDepartment of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, ChinaDepartment of General Surgery (Pancreatic Hepatobiliary Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, ChinaDepartment of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, ChinaDepartment of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, ChinaDepartment of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, ChinaDepartment of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, ChinaDepartment of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, ChinaDepartment of General Surgery (Pancreatic Hepatobiliary Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, ChinaPDAC is one of the most common malignant tumors worldwide. The difficulty of early diagnosis and lack of effective treatment are the main reasons for its poor prognosis. Therefore, it is urgent to identify novel diagnostic and therapeutic targets for PDAC patients. The m<sup>7</sup>G methylation is a common type of RNA modification that plays a pivotal role in regulating tumor development. However, the correlation between m<sup>7</sup>G regulatory genes and PDAC progression remains unclear. By integrating gene expression and related clinical information of PDAC patients from TCGA and GEO cohorts, m<sup>7</sup>G binding protein NCBP2 was found to be highly expressed in PDAC patients. More importantly, PDAC patients with high NCBP2 expression had a worse prognosis. Stable NCBP2-knockdown and overexpression PDAC cell lines were constructed to further perform in-vitro and in-vivo experiments. NCBP2-knockdown significantly inhibited PDAC cell proliferation, while overexpression of NCBP2 dramatically promoted PDAC cell growth. Mechanistically, NCBP2 enhanced the translation of c-JUN, which in turn activated MEK/ERK signaling to promote PDAC progression. In conclusion, our study reveals that m<sup>7</sup>G reader NCBP2 promotes PDAC progression by activating MEK/ERK pathway, which could serve as a novel therapeutic target for PDAC patients.https://www.mdpi.com/2072-6694/15/22/5454m<sup>7</sup>G methylationNCBP2MEK/ERKc-JUNpancreatic adenocarcinoma |
| spellingShingle | Jiancong Xie Taiwei Mo Ruibing Li Hao Zhang Guanzhan Liang Tao Ma Jing Chen Hanlin Xie Xiaofeng Wen Tuo Hu Zhenyu Xian Weidong Pan The m<sup>7</sup>G Reader NCBP2 Promotes Pancreatic Cancer Progression by Upregulating MAPK/ERK Signaling Cancers m<sup>7</sup>G methylation NCBP2 MEK/ERK c-JUN pancreatic adenocarcinoma |
| title | The m<sup>7</sup>G Reader NCBP2 Promotes Pancreatic Cancer Progression by Upregulating MAPK/ERK Signaling |
| title_full | The m<sup>7</sup>G Reader NCBP2 Promotes Pancreatic Cancer Progression by Upregulating MAPK/ERK Signaling |
| title_fullStr | The m<sup>7</sup>G Reader NCBP2 Promotes Pancreatic Cancer Progression by Upregulating MAPK/ERK Signaling |
| title_full_unstemmed | The m<sup>7</sup>G Reader NCBP2 Promotes Pancreatic Cancer Progression by Upregulating MAPK/ERK Signaling |
| title_short | The m<sup>7</sup>G Reader NCBP2 Promotes Pancreatic Cancer Progression by Upregulating MAPK/ERK Signaling |
| title_sort | m sup 7 sup g reader ncbp2 promotes pancreatic cancer progression by upregulating mapk erk signaling |
| topic | m<sup>7</sup>G methylation NCBP2 MEK/ERK c-JUN pancreatic adenocarcinoma |
| url | https://www.mdpi.com/2072-6694/15/22/5454 |
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