&lt;b&gt;&lt;i&gt;RAP1GAP&lt;/i&gt;&lt;/b&gt; Functions as a Tumor Suppressor Gene and Is Regulated by DNA Methylation in Differentiated Thyroid Cancer

Faam, Bita; Ghaffari, Mohammad Ali; Khorsandi, Layasadat; Ghadiri, Ata; Totonchi, Mehdi; Amouzegar, Atieh; Fanaei, Seyed Ahmad; Azizi, Fereidoun; Shahbazian, Hajeih B; Tabar, Mahmoud Hashemi

doi:10.1159/000516122

Cited by 8 publications

(6 citation statements)

References 29 publications

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“…However, either PTX or TSAIII also revealed the prohibited activity on Rap1-GAP. A study shows Rap1GAP as a tumor suppressor can inhibit the development and progression of many tumors [ 33 , 34 ]. Therefore, the balance of RasGRP2 and RAP1 with Rap1-GAP will decide the tumor direction.…”

Section: Discussionmentioning

confidence: 99%

Timosaponin AIII Suppresses RAP1 Signaling Pathway to Enhance the Inhibitory Effect of Paclitaxel on Nasopharyngeal Carcinoma

Zhou

et al. 2022

Computational and Mathematical Methods in Medicine

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Although PTX has been identified as an effective drug for nasopharyngeal carcinoma (NPC) therapy, it has serious side effects in the human body. Previous studies have shown that timosaponin AIII (TSAIII) can inhibit the malignant progression of NPC cells. This study investigated the active mechanism of the combination of TSAIII and paclitaxel (PTX) on NPC. Cellular viability, apoptosis, apoptotic factors, and RAP1 signaling regulators were detected in the PNC cells (CNE-1 and HNE-2) and the subcutaneous CNE-1 transplanted nude mice treated with PTX or/and TSAIII. The results showed that TSAIII notably strengthened the inhibitory effect of PTX on the proliferation of NPC cells CNE-1 and HNE-2; upregulated the expression of Bax B-cell lymphoma 2 (Bcl-2)/Bcl-xL-associated death promoter (Bad), and Ras-associated protein1 (RAP1) GTPase activating protein (Rap1GAP); inhibited the level of Bcl-2, RAP1, and Ras guanine nucleotide releasing protein (RasGRP2); and significantly enhanced the promoting effect of PTX on apoptosis in the CNE-1 and HNE-2 cells. Besides, TSAIII strengthened the inhibitory effect of PTX on xenograft tumor in nude mice without adverse reactions. In conclusion, the combination administration of TSAIII and PTX had a significantly therapeutic effect on NPC and avoided the PTX’s side effects, which may have acted as a new direction for the study of therapeutic approaches for NPC clinically.

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Section: Discussionmentioning

confidence: 99%

Timosaponin AIII Suppresses RAP1 Signaling Pathway to Enhance the Inhibitory Effect of Paclitaxel on Nasopharyngeal Carcinoma

Zhou

et al. 2022

Computational and Mathematical Methods in Medicine

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“…The role of ADH1C in pancreatic cancer is rarely reported and needs further study. Tumor suppressor gene RAP1GAP, which is inactivated by hypermethylation of its regulatory region, can cause thyroid tumor [ 56 ]. The silencing of RAP1GAP promotes endometrioid adenocarcinoma cell migration and invasion [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of bulk and single-cell transcriptomic data reveals a novel signature associated with endoplasmic reticulum stress, lipid metabolism, and liver metastasis in pancreatic cancer

Liu,

Ren,

Fang

et al. 2024

J Transl Med

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Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with high probability of recurrence and distant metastasis. Liver metastasis is the predominant metastatic mode developed in most pancreatic cancer cases, which seriously affects the overall survival rate of patients. Abnormally activated endoplasmic reticulum stress and lipid metabolism reprogramming are closely related to tumor growth and metastasis. This study aims to construct a prognostic model based on endoplasmic reticulum stress and lipid metabolism for pancreatic cancer, and further explore its correlation with tumor immunity and the possibility of immunotherapy. Methods Transcriptomic and clinical data are acquired from TCGA, ICGC, and GEO databases. Potential prognostic genes were screened by consistent clustering and WGCNA methods, and the whole cohort was randomly divided into training and testing groups. The prognostic model was constructed by machine learning method in the training cohort and verified in the test, TCGA and ICGC cohorts. The clinical application of this model and its relationship with tumor immunity were analyzed, and the relationship between endoplasmic reticulum stress and intercellular communication was further explored. Results A total of 92 characteristic genes related to endoplasmic reticulum stress, lipid metabolism and liver metastasis were identified in pancreatic cancer. We established and validated a prognostic model for pancreatic cancer with 7 signatures, including ADH1C, APOE, RAP1GAP, NPC1L1, P4HB, SOD2, and TNFSF10. This model is considered to be an independent prognosticator and is a more accurate predictor of overall survival than age, gender, and stage. TIDE score was increased in high-risk group, while the infiltration levels of CD8+ T cells and M1 macrophages were decreased. The number and intensity of intercellular communication were increased in the high ER stress group. Conclusions We constructed and validated a novel prognostic model for pancreatic cancer, which can also be used as an instrumental variable to predict the prognosis and immune microenvironment. In addition, this study revealed the effect of ER stress on cell–cell communication in the tumor microenvironment.

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“…Abnormal DNA methylation is also a common mechanism that can regulate gene transcription. Abnormal DNA methylation levels have been found in some malignancies, such as breast (Győrffy et al 2016), thyroid (Faam et al 2021), liver (Li et al 2019), and lung cancers (Hong and Kim 2021), and affect tumor progression and prognosis. Our ndings that increased DNA methylation levels in some tumor types, especially in BLCA and HNSC, which may be one of the reasons for the downregulation of DLAT expression in these tumors.…”

Section: Discussionmentioning

confidence: 99%

Cuproptosis-related gene DLAT is a prognostic and immunological biomarker in pan-cancer

Zeng

Fang

et al. 2023

Preprint

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Dihydrolipoamide S-acetyltrans-ferase (DLAT), a mitochondrial protein involved in glucose metabolism, has been identified as a key gene associated with cuproptosis recently. However, studies on DLAT in pan-cancer have not been found. Aim of this study is to explore the expression profiles and clinical value of DLAT in pan-cancer. DLAT expression profiles were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), UALCAN and the Human Protein Atlas (HPA) websites. The prognostic and diagnostic values of DLAT and its relationship with immune cell infiltration were analyzed based on TCGA data. cBioPortal and UALCAN websites were used to search gene alteration and methylation status of DLAT in tumors, respectively. CancerSEA database was used to investigate the biological functions of DLAT at the single-cell level. Finally, STRING, GAPIA2.0 and TIMER databases were used to construct protein-protein interaction (PPI) networks and functional enrichment analyses. High DLAT expression was found in most cancers and predicted poor prognosis in patients with several tumors, such as breast cancer, esophageal cancer, head and neck squamous cell carcinoma. DLAT showed early diagnostic value in 17 tumors, especially in acute myeloid leukemia (LAML). Abnormal gene alterations and DNA methylation of DLAT were verified in pan-cancer. Single cell RNA sequencing (scRNAseq) analysis reflected that DLAT could regulate various biological functions of cancer cells. Abnormal expression of DLAT regulated infiltration of multiple immune cells in a variety of tumors. Gene enrichment analysis showed that DLAT was involved in mitochondrial matrix, coated vesicle and ribonucleoprotein granule. DLAT can be used as an important indicator of early diagnosis, prognosis and immunotherapy for a variety of tumors.

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<b><i>RAP1GAP</i></b> Functions as a Tumor Suppressor Gene and Is Regulated by DNA Methylation in Differentiated Thyroid Cancer

Cited by 8 publications

References 29 publications

Timosaponin AIII Suppresses RAP1 Signaling Pathway to Enhance the Inhibitory Effect of Paclitaxel on Nasopharyngeal Carcinoma

Timosaponin AIII Suppresses RAP1 Signaling Pathway to Enhance the Inhibitory Effect of Paclitaxel on Nasopharyngeal Carcinoma

Comprehensive analysis of bulk and single-cell transcriptomic data reveals a novel signature associated with endoplasmic reticulum stress, lipid metabolism, and liver metastasis in pancreatic cancer

Cuproptosis-related gene DLAT is a prognostic and immunological biomarker in pan-cancer

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