M6A-Related Long Non-Coding RNA Displays Utility in Predicting Prognosis, Portraying the Tumor Immune Microenvironment and Guiding Immunotherapy in Pancreatic Ductal Adenocarcinoma
N6-methyladenosine (m6A) lncRNA plays a pivotal role in cancer. However, little is known about its role in pancreatic ductal adenocarcinoma (PDAC) and its tumor immune microenvironment (TIME). Based on The Cancer Genome Atlas (TCGA) cohort, m6A-related lncRNAs (m6A-lncRNA) with prognostic value were...
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MDPI AG
2023-02-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/11/3/499 |
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| author | Guangyu Xu Yutian Ji Lufeng Wang Hao Xu Chaodong Shen Haihao Ye Xiangchou Yang |
| author_facet | Guangyu Xu Yutian Ji Lufeng Wang Hao Xu Chaodong Shen Haihao Ye Xiangchou Yang |
| author_sort | Guangyu Xu |
| collection | DOAJ |
| description | N6-methyladenosine (m6A) lncRNA plays a pivotal role in cancer. However, little is known about its role in pancreatic ductal adenocarcinoma (PDAC) and its tumor immune microenvironment (TIME). Based on The Cancer Genome Atlas (TCGA) cohort, m6A-related lncRNAs (m6A-lncRNA) with prognostic value were filtered using Pearson analysis and univariate Cox regression analysis. Distinct m6A-lncRNA subtypes were divided using unsupervised consensus clustering. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to establish an m6A-lncRNA-based risk score signature. The CIBERSORT and ESTIMATE algorithms were employed to analyze the TIME. The expression pattern of TRAF3IP2-AS1 was examined using qRT-PCR. The influence of TRAF3IP2-AS1 knockdown on cell proliferation was estimated by performing CCK8, EdU and colony-formation assays. Flow cytometry was applied to measure the effect of TRAF3IP2-AS1 knockdown on cell cycle and apoptosis. The in vivo anti-tumor effect of TRAF3IP2-AS1 was validated in a tumor-bearing mouse model. Two m6A-lncRNA subtypes with different TIME features were clarified. A risk score signature was constructed as a prognostic predictor based on m6A-lncRNAs. The risk score also correlated with TIME characterization, which facilitated immunotherapy. Finally, the m6A-lncRNA TRAF3IP2-AS1 was proved to be a tumor suppressor in PDAC. We comprehensively demonstrated m6A-lncRNAs to be useful tools for prognosis prediction, TIME depiction and immunotherapeutic guidance in PDAC. |
| first_indexed | 2024-03-11T05:48:27Z |
| format | Article |
| id | doaj.art-b2ece27eba8541a9ad631b8ca916cf54 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-11T05:48:27Z |
| publishDate | 2023-02-01 |
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| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-b2ece27eba8541a9ad631b8ca916cf542023-11-17T14:16:54ZengMDPI AGVaccines2076-393X2023-02-0111349910.3390/vaccines11030499M6A-Related Long Non-Coding RNA Displays Utility in Predicting Prognosis, Portraying the Tumor Immune Microenvironment and Guiding Immunotherapy in Pancreatic Ductal AdenocarcinomaGuangyu Xu0Yutian Ji1Lufeng Wang2Hao Xu3Chaodong Shen4Haihao Ye5Xiangchou Yang6Department of Hematology and Medical Oncology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, ChinaDepartment of Hematology and Medical Oncology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, ChinaNeurology Department, East Hospital, Tongji University, Shanghai 310000, ChinaDepartment of Hematology and Medical Oncology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, ChinaDepartment of Cardiology, Wenzhou Traditional Chinese Medicine Hospital, Wenzhou 325000, ChinaDepartment of Hematology and Medical Oncology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, ChinaN6-methyladenosine (m6A) lncRNA plays a pivotal role in cancer. However, little is known about its role in pancreatic ductal adenocarcinoma (PDAC) and its tumor immune microenvironment (TIME). Based on The Cancer Genome Atlas (TCGA) cohort, m6A-related lncRNAs (m6A-lncRNA) with prognostic value were filtered using Pearson analysis and univariate Cox regression analysis. Distinct m6A-lncRNA subtypes were divided using unsupervised consensus clustering. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to establish an m6A-lncRNA-based risk score signature. The CIBERSORT and ESTIMATE algorithms were employed to analyze the TIME. The expression pattern of TRAF3IP2-AS1 was examined using qRT-PCR. The influence of TRAF3IP2-AS1 knockdown on cell proliferation was estimated by performing CCK8, EdU and colony-formation assays. Flow cytometry was applied to measure the effect of TRAF3IP2-AS1 knockdown on cell cycle and apoptosis. The in vivo anti-tumor effect of TRAF3IP2-AS1 was validated in a tumor-bearing mouse model. Two m6A-lncRNA subtypes with different TIME features were clarified. A risk score signature was constructed as a prognostic predictor based on m6A-lncRNAs. The risk score also correlated with TIME characterization, which facilitated immunotherapy. Finally, the m6A-lncRNA TRAF3IP2-AS1 was proved to be a tumor suppressor in PDAC. We comprehensively demonstrated m6A-lncRNAs to be useful tools for prognosis prediction, TIME depiction and immunotherapeutic guidance in PDAC.https://www.mdpi.com/2076-393X/11/3/499N6-methyladenosinelncRNApancreatic ductal adenocarcinomatumor immunologytumor immune microenvironmentimmunotherapy |
| spellingShingle | Guangyu Xu Yutian Ji Lufeng Wang Hao Xu Chaodong Shen Haihao Ye Xiangchou Yang M6A-Related Long Non-Coding RNA Displays Utility in Predicting Prognosis, Portraying the Tumor Immune Microenvironment and Guiding Immunotherapy in Pancreatic Ductal Adenocarcinoma Vaccines N6-methyladenosine lncRNA pancreatic ductal adenocarcinoma tumor immunology tumor immune microenvironment immunotherapy |
| title | M6A-Related Long Non-Coding RNA Displays Utility in Predicting Prognosis, Portraying the Tumor Immune Microenvironment and Guiding Immunotherapy in Pancreatic Ductal Adenocarcinoma |
| title_full | M6A-Related Long Non-Coding RNA Displays Utility in Predicting Prognosis, Portraying the Tumor Immune Microenvironment and Guiding Immunotherapy in Pancreatic Ductal Adenocarcinoma |
| title_fullStr | M6A-Related Long Non-Coding RNA Displays Utility in Predicting Prognosis, Portraying the Tumor Immune Microenvironment and Guiding Immunotherapy in Pancreatic Ductal Adenocarcinoma |
| title_full_unstemmed | M6A-Related Long Non-Coding RNA Displays Utility in Predicting Prognosis, Portraying the Tumor Immune Microenvironment and Guiding Immunotherapy in Pancreatic Ductal Adenocarcinoma |
| title_short | M6A-Related Long Non-Coding RNA Displays Utility in Predicting Prognosis, Portraying the Tumor Immune Microenvironment and Guiding Immunotherapy in Pancreatic Ductal Adenocarcinoma |
| title_sort | m6a related long non coding rna displays utility in predicting prognosis portraying the tumor immune microenvironment and guiding immunotherapy in pancreatic ductal adenocarcinoma |
| topic | N6-methyladenosine lncRNA pancreatic ductal adenocarcinoma tumor immunology tumor immune microenvironment immunotherapy |
| url | https://www.mdpi.com/2076-393X/11/3/499 |
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