Comprehensive analysis to identify a novel PTEN-associated ceRNA regulatory network as a prognostic biomarker for lung adenocarcinoma
Lung adenocarcinoma (LUAD) is one of the most prevalent forms of lung cancer. Competitive endogenous RNA (ceRNA) plays an important role in the pathogenesis of lung cancer. Phosphatase and tensin homolog (PTEN) is one of the most frequently deleted tumour suppressor genes in LUAD. The present study...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.923026/full |
| _version_ | 1828148796410822656 |
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| author | Rui Xin Biao Shen Ying-Jie Jiang Ji-Bin Liu Sha Li Li-Kun Hou Wei Wu Cheng-You Jia Chun-Yan Wu Da Fu Da Fu Yu-Shui Ma Yu-Shui Ma Geng-Xi Jiang |
| author_facet | Rui Xin Biao Shen Ying-Jie Jiang Ji-Bin Liu Sha Li Li-Kun Hou Wei Wu Cheng-You Jia Chun-Yan Wu Da Fu Da Fu Yu-Shui Ma Yu-Shui Ma Geng-Xi Jiang |
| author_sort | Rui Xin |
| collection | DOAJ |
| description | Lung adenocarcinoma (LUAD) is one of the most prevalent forms of lung cancer. Competitive endogenous RNA (ceRNA) plays an important role in the pathogenesis of lung cancer. Phosphatase and tensin homolog (PTEN) is one of the most frequently deleted tumour suppressor genes in LUAD. The present study aimed to identify a novel PTEN-associated-ceRNA regulatory network and identify potential prognostic markers associated with LUAD. Transcriptome sequencing profiles of 533 patients with LUAD were obtained from TCGA database, and differentially expressed genes (DEGs) were screened in LUAD samples with PTEN high- (PTENhigh) and low- (PTENlow) expression. Eventually, an important PTEN-related marker was identified, namely, the LINC00460/miR-150-3p axis. Furthermore, the predicted target genes (EME1/HNRNPAB/PLAUR/SEMA3A) were closely related to overall survival and prognosis. The LINC00460/miR-150-3p axis was identified as a clinical prognostic factor through Cox regression analysis. Methylation analyses suggested that abnormal regulation of the predicted target genes might be caused by hypomethylation. Furthermore, immune infiltration analysis showed that the LINC00460/miR-150-3p axis could alter the levels of immune infiltration in the tumour immune microenvironment, and promote the clinical progression of LUAD. To specifically induce PTEN deletion in the lungs, we constructed an STP mouse model (SFTPC-rtTA/tetO-cre/Ptenflox/+). Quantitative PCR (qPCR) and immunohistochemical (IHC) analysis were used to detect predicted target genes. Therefore, we revealed that the PTEN-related LINC00460/miR-150-3p axis based on ceRNA mechanism plays an important role in the development of LUAD and provides a new direction and theoretical basis for its targeted therapy. |
| first_indexed | 2024-04-11T21:20:49Z |
| format | Article |
| id | doaj.art-ea47b5d55e9c46e4b5e95f850666b3f2 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T21:20:49Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-ea47b5d55e9c46e4b5e95f850666b3f22022-12-22T04:02:37ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-08-011210.3389/fonc.2022.923026923026Comprehensive analysis to identify a novel PTEN-associated ceRNA regulatory network as a prognostic biomarker for lung adenocarcinomaRui Xin0Biao Shen1Ying-Jie Jiang2Ji-Bin Liu3Sha Li4Li-Kun Hou5Wei Wu6Cheng-You Jia7Chun-Yan Wu8Da Fu9Da Fu10Yu-Shui Ma11Yu-Shui Ma12Geng-Xi Jiang13Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Thoracic Surgery, Affiliated Tumor Hospital of Nantong University, Nantong, ChinaDepartment of Pathology, Navy Military Medical University Affiliated Changhai Hospital, Shanghai, ChinaInstitute of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu, ChinaDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaInstitute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaCancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Thoracic Surgery, Navy Military Medical University Affiliated Changhai Hospital, Shanghai, ChinaLung adenocarcinoma (LUAD) is one of the most prevalent forms of lung cancer. Competitive endogenous RNA (ceRNA) plays an important role in the pathogenesis of lung cancer. Phosphatase and tensin homolog (PTEN) is one of the most frequently deleted tumour suppressor genes in LUAD. The present study aimed to identify a novel PTEN-associated-ceRNA regulatory network and identify potential prognostic markers associated with LUAD. Transcriptome sequencing profiles of 533 patients with LUAD were obtained from TCGA database, and differentially expressed genes (DEGs) were screened in LUAD samples with PTEN high- (PTENhigh) and low- (PTENlow) expression. Eventually, an important PTEN-related marker was identified, namely, the LINC00460/miR-150-3p axis. Furthermore, the predicted target genes (EME1/HNRNPAB/PLAUR/SEMA3A) were closely related to overall survival and prognosis. The LINC00460/miR-150-3p axis was identified as a clinical prognostic factor through Cox regression analysis. Methylation analyses suggested that abnormal regulation of the predicted target genes might be caused by hypomethylation. Furthermore, immune infiltration analysis showed that the LINC00460/miR-150-3p axis could alter the levels of immune infiltration in the tumour immune microenvironment, and promote the clinical progression of LUAD. To specifically induce PTEN deletion in the lungs, we constructed an STP mouse model (SFTPC-rtTA/tetO-cre/Ptenflox/+). Quantitative PCR (qPCR) and immunohistochemical (IHC) analysis were used to detect predicted target genes. Therefore, we revealed that the PTEN-related LINC00460/miR-150-3p axis based on ceRNA mechanism plays an important role in the development of LUAD and provides a new direction and theoretical basis for its targeted therapy.https://www.frontiersin.org/articles/10.3389/fonc.2022.923026/fullceRNA networkLINC00460miR-150-3pLUADPTEN |
| spellingShingle | Rui Xin Biao Shen Ying-Jie Jiang Ji-Bin Liu Sha Li Li-Kun Hou Wei Wu Cheng-You Jia Chun-Yan Wu Da Fu Da Fu Yu-Shui Ma Yu-Shui Ma Geng-Xi Jiang Comprehensive analysis to identify a novel PTEN-associated ceRNA regulatory network as a prognostic biomarker for lung adenocarcinoma Frontiers in Oncology ceRNA network LINC00460 miR-150-3p LUAD PTEN |
| title | Comprehensive analysis to identify a novel PTEN-associated ceRNA regulatory network as a prognostic biomarker for lung adenocarcinoma |
| title_full | Comprehensive analysis to identify a novel PTEN-associated ceRNA regulatory network as a prognostic biomarker for lung adenocarcinoma |
| title_fullStr | Comprehensive analysis to identify a novel PTEN-associated ceRNA regulatory network as a prognostic biomarker for lung adenocarcinoma |
| title_full_unstemmed | Comprehensive analysis to identify a novel PTEN-associated ceRNA regulatory network as a prognostic biomarker for lung adenocarcinoma |
| title_short | Comprehensive analysis to identify a novel PTEN-associated ceRNA regulatory network as a prognostic biomarker for lung adenocarcinoma |
| title_sort | comprehensive analysis to identify a novel pten associated cerna regulatory network as a prognostic biomarker for lung adenocarcinoma |
| topic | ceRNA network LINC00460 miR-150-3p LUAD PTEN |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.923026/full |
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