Systemic Analyses of Cuproptosis-Related lncRNAs in Pancreatic Adenocarcinoma, with a Focus on the Molecular Mechanism of LINC00853
Pancreatic cancer (PC) is a deadly malignant digestive tumor with poor prognoses and a lack of effective treatment options. Cuproptosis, a recently identified copper-dependent programmed cell death type, has been implicated in multiple cancers. Long non-coding RNAs (lncRNAs) are also linked to the p...
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/9/7923 |
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| author | Leifeng Chen Lin Zhang Haihua He Fei Shao Yibo Gao Jie He |
| author_facet | Leifeng Chen Lin Zhang Haihua He Fei Shao Yibo Gao Jie He |
| author_sort | Leifeng Chen |
| collection | DOAJ |
| description | Pancreatic cancer (PC) is a deadly malignant digestive tumor with poor prognoses and a lack of effective treatment options. Cuproptosis, a recently identified copper-dependent programmed cell death type, has been implicated in multiple cancers. Long non-coding RNAs (lncRNAs) are also linked to the progression of PC. However, the role and prognostic values of cuproptosis-related lncRNAs in pancreatic adenocarcinoma (PAAD) remain unclear. In this study, we systemically analyzed the differential expressions and prognostic values of 672 cuproptosis-related lncRNAs in PAAD. Based on this, a prognostic signature including four lncRNAs (<i>LINC00853</i>, <i>AC099850.3</i>, <i>AC010719.1</i>, and <i>AC006504.7</i>) was constructed and was able to divide PAAD patients into high- and low-risk groups with significantly different prognoses. Next, we focused on lncRNA <i>LINC00853</i>. The differential expressions of LINC00853 between normal tissue and PAAD samples were validated by qRT-PCR. LINC00853 was knocked down by siRNA in PC cell lines BxPC-3 and PANC-1 and the oncogenic role of LINC00853 was validated by CCK8, colony formation, and EdU assays. Subsequently, LINC00853 knockdown cells were subjected to tumor xenograft tests and exhibited decreased tumor growth in nude mice. Mechanistically, knockdown of LINC00853 significantly reduced cellular glycolysis and enhanced cellular mitochondrial respiration levels in PC cells. Moreover, knockdown of LINC00853 decreased the protein level of a glycolytic kinase PFKFB3. Finally, glycolysis tests and functional tests using LINC00853 and HA-PFKFB3 indicated that the effects of LINC00853 on glycolysis and cell proliferation were mediated by PFKFB3. In conclusion, our systemic analyses have highlighted the important roles of cuproptosis-related lncRNAs in PAAD while the prognostic signature based on them showed excellent performance in PAAD patients and is expected to provide clinical guidance for individualized treatment. In addition, our findings provide a novel mechanism by which the LINC00853-PFKFB3 axis critically regulates aerobic glycolysis and cell proliferation in PC cells. |
| first_indexed | 2024-03-11T04:17:32Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:17:32Z |
| publishDate | 2023-04-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d2a7eb5fa87a413dab316389e57696f82023-11-17T23:02:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01249792310.3390/ijms24097923Systemic Analyses of Cuproptosis-Related lncRNAs in Pancreatic Adenocarcinoma, with a Focus on the Molecular Mechanism of LINC00853Leifeng Chen0Lin Zhang1Haihua He2Fei Shao3Yibo Gao4Jie He5Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaCentral Laboratory & Shenzhen Key Laboratory of Epigenetics and Precision Medicine for Cancers, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, ChinaDepartment of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaPancreatic cancer (PC) is a deadly malignant digestive tumor with poor prognoses and a lack of effective treatment options. Cuproptosis, a recently identified copper-dependent programmed cell death type, has been implicated in multiple cancers. Long non-coding RNAs (lncRNAs) are also linked to the progression of PC. However, the role and prognostic values of cuproptosis-related lncRNAs in pancreatic adenocarcinoma (PAAD) remain unclear. In this study, we systemically analyzed the differential expressions and prognostic values of 672 cuproptosis-related lncRNAs in PAAD. Based on this, a prognostic signature including four lncRNAs (<i>LINC00853</i>, <i>AC099850.3</i>, <i>AC010719.1</i>, and <i>AC006504.7</i>) was constructed and was able to divide PAAD patients into high- and low-risk groups with significantly different prognoses. Next, we focused on lncRNA <i>LINC00853</i>. The differential expressions of LINC00853 between normal tissue and PAAD samples were validated by qRT-PCR. LINC00853 was knocked down by siRNA in PC cell lines BxPC-3 and PANC-1 and the oncogenic role of LINC00853 was validated by CCK8, colony formation, and EdU assays. Subsequently, LINC00853 knockdown cells were subjected to tumor xenograft tests and exhibited decreased tumor growth in nude mice. Mechanistically, knockdown of LINC00853 significantly reduced cellular glycolysis and enhanced cellular mitochondrial respiration levels in PC cells. Moreover, knockdown of LINC00853 decreased the protein level of a glycolytic kinase PFKFB3. Finally, glycolysis tests and functional tests using LINC00853 and HA-PFKFB3 indicated that the effects of LINC00853 on glycolysis and cell proliferation were mediated by PFKFB3. In conclusion, our systemic analyses have highlighted the important roles of cuproptosis-related lncRNAs in PAAD while the prognostic signature based on them showed excellent performance in PAAD patients and is expected to provide clinical guidance for individualized treatment. In addition, our findings provide a novel mechanism by which the LINC00853-PFKFB3 axis critically regulates aerobic glycolysis and cell proliferation in PC cells.https://www.mdpi.com/1422-0067/24/9/7923pancreatic cancerlncRNA LINC00853aerobic glycolysisprognostic signaturecuproptosis |
| spellingShingle | Leifeng Chen Lin Zhang Haihua He Fei Shao Yibo Gao Jie He Systemic Analyses of Cuproptosis-Related lncRNAs in Pancreatic Adenocarcinoma, with a Focus on the Molecular Mechanism of LINC00853 International Journal of Molecular Sciences pancreatic cancer lncRNA LINC00853 aerobic glycolysis prognostic signature cuproptosis |
| title | Systemic Analyses of Cuproptosis-Related lncRNAs in Pancreatic Adenocarcinoma, with a Focus on the Molecular Mechanism of LINC00853 |
| title_full | Systemic Analyses of Cuproptosis-Related lncRNAs in Pancreatic Adenocarcinoma, with a Focus on the Molecular Mechanism of LINC00853 |
| title_fullStr | Systemic Analyses of Cuproptosis-Related lncRNAs in Pancreatic Adenocarcinoma, with a Focus on the Molecular Mechanism of LINC00853 |
| title_full_unstemmed | Systemic Analyses of Cuproptosis-Related lncRNAs in Pancreatic Adenocarcinoma, with a Focus on the Molecular Mechanism of LINC00853 |
| title_short | Systemic Analyses of Cuproptosis-Related lncRNAs in Pancreatic Adenocarcinoma, with a Focus on the Molecular Mechanism of LINC00853 |
| title_sort | systemic analyses of cuproptosis related lncrnas in pancreatic adenocarcinoma with a focus on the molecular mechanism of linc00853 |
| topic | pancreatic cancer lncRNA LINC00853 aerobic glycolysis prognostic signature cuproptosis |
| url | https://www.mdpi.com/1422-0067/24/9/7923 |
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