Pan-Cancer Analysis Reveals SH3TC2 as an Oncogene for Colorectal Cancer and Promotes Tumorigenesis via the MAPK Pathway

Huang, Chengzhi; Ye, Hui; Zhou, Yue; Zhang, Qing; Yao, Xueqing

doi:10.3390/cancers14153735

Cited by 13 publications

(11 citation statements)

References 61 publications

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“…The MAPK signalling pathway can transduce extracellular signals into the nucleus and has been reported to regulate the proliferation, apoptosis, migration, invasion, and chemoresistance of colon cancer cells [25][26][27][28]. The RAF/MEK/ERK signal transduction cascade is a classical MAPK pathway that can regulate cell proliferation, motility, and survival in various pathological and physiological processes.…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin Enhances the Effects of Oxaliplatin by Activating PDCD5/ARAF mediated Signal Transduction in Colon Cancer

Peng,

Zheng,

Qiu

et al. 2023

Preprint

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Programmed cell death 5 (PDCD5) has been reported to be expressed at low levels in various types of cancers and can be upregulated and rapidly migrate from the cytoplasm to the nucleus when cell death is induced. It is believed to be an important prognostic marker for the response to cancer therapy. Further study of the molecular mechanism by which PDCD5 exerts its antitumour activity and exploration of low toxicity and high-efficiency drugs targeting PDCD5 may reveal a promising strategy for clinical cancer therapy. In this study, the function and molecular mechanism of PDCD5 in colon tumorigenesis were thoroughly studied. PDCD5 was distributed mainly in nontumor tissues and expressed at low levels in colon cancer tissues, and the expression level of PDCD5 was negatively related to cell proliferation and tumour growth. In addition, PDCD5 expression was positively related to the cytotoxicity of oxaliplatin and dihydroartemisinin (DHA). The molecular mechanism of PDCD5 in colon tumorigenesis was also studied using proteomic analysis, which showed that PDCD5 can downregulate ARAF expression and subsequently impair ARAF/MEK/ERK signal transduction. DHA exerts its antitumour activity via active PDCD5 to suppress the ARAF/MEK/ERK signalling pathway and improve the antitumour effects of oxaliplatin. In summary, DHA can enhance the cytotoxic effects of oxaliplatin by regulating PDCD5 expression and subcellular localization to suppress the ARAF/MEK/ERK signalling pathway.

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Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin Enhances the Effects of Oxaliplatin by Activating PDCD5/ARAF mediated Signal Transduction in Colon Cancer

Peng,

Zheng,

Qiu

et al. 2023

Preprint

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“…The rest group of genes that were significantly upregulated in HIF-2-altered tumors are involved in urothelial differentiation ( UPK2 ) [ 33 ], stemness ( GPR78, HS3ST2 ) [ 34 , 35 ], epithelial-mesenchymal transition (CRYBG2) [ 36 ], PI3K/Akt/beta-catenin signaling ( VGLL1 ) [ 37 ], MAPK signaling (SH3TC2, GAREM1) [ 38 , 39 ], coactivation of different nuclear receptors ( NCOA1 ) [ 40 ], ER stress and hedgehog signaling ( CREB3L2 ) [ 41 ], TGF-beta and WNT signaling (CRYBG2) [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Inducible Factor-2-Altered Urothelial Carcinoma: Clinical and Genomic Features

et al. 2022

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Background: Hypoxia is recognized as a key feature of cancer growth and is involved in various cellular processes, including proliferation, angiogenesis, and immune surveillance. Besides hypoxia-inducible factor 1-alpha (HIF-1α), which is the main mediator of hypoxia effects and can also be activated under normoxic conditions, little is known about its counterpart, HIF-2. This study focused on investigating the clinical and molecular landscape of HIF-2-altered urothelial carcinoma (UC). Methods: Publicly available next-generation sequencing (NGS) data from muscle-invasive UC cell lines and patient tumor samples from the MSK/TCGA 2020 cohort (n = 476) were interrogated for the level of expression (mRNA, protein) and presence of mutations, copy number variations, structural variants in the EPAS1 gene encoding HIF-2, and findings among various clinical (stage, grade, progression-free and overall survival) and molecular (tumor mutational burden, enriched gene expression) parameters were compared between altered and unaltered tumors. Results: 19% (7/37) of UC cell lines and 7% (27/380) of patients with muscle-invasive UC display high EPAS1 mRNA and protein expression or/and EPAS1 alterations. EPAS1-altered tumors are associated with higher stage, grade, and lymph node metastasis as well as with shorter PFS (14 vs. 51 months, q = 0.01) and OS (15 vs. 55 months, q = 0.01). EPAS1 mRNA expression is directly correlated with that of its target-genes, including VEGF, FLT1, KDR, DLL4, CDH5, ANGPT1 (q < 0.001). While there is a slightly higher tumor mutational burden in EPAS1-altered tumors (9.9 vs. 4.9 mut/Mb), they are enriched in and associated with genes promoting immune evasion, including ARID5B, SPINT1, AAK1, CLIC3, SORT1, SASH1, and FGFR3, respectively (q < 0.001). Conclusions: HIF-2-altered UC has an aggressive clinical and a distinct genomic and immunogenomic profile enriched in angiogenesis- and immune evasion-preventing genes.

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“…In this study, we collected three cohorts from public databases. Among them, mRNA expression data of GBM patients were obtained from the TCGA ( https://portal.gdc.cancer.gov/ ) [ 15 ], GTEx ( https://xenabrowser.net/datapages/ ) [ 16 ], and CGGA ( http://www.cgga.org.cn/ ) databases [ 17 , 18 ]. Clinical data obtained from TCGA and CGGA databases were shown in Additional file 3 : Table S1.…”

Section: Methodsmentioning

confidence: 99%

Identification and validation of a novel prognostic signature based on mitochondria and oxidative stress related genes for glioblastoma

Tong

Xia

et al. 2023

J Transl Med

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Background Mitochondria represent a major source of reactive oxygen species (ROS) in cells, and the direct increase in ROS content is the primary cause of oxidative stress, which plays an important role in tumor proliferation, invasion, angiogenesis, and treatment. However, the relationship between mitochondrial oxidative stress-related genes and glioblastoma (GBM) remains unclear. This study aimed to investigate the value of mitochondria and oxidative stress-related genes in the prognosis and therapeutic targets of GBM. Methods We retrieved mitochondria and oxidative stress-related genes from several public databases. The LASSO regression and Cox analyses were utilized to build a risk model and the ROC curve was used to assess its performance. Then, we analyzed the correlation between the model and immunity and mutation. Furthermore, CCK8 and EdU assays were utilized to verify the proliferative capacity of GBM cells and flow cytometry was used to analyze apoptosis rates. Finally, the JC-1 assay and ATP levels were utilized to detect mitochondrial function, and the intracellular ROS levels were determined using MitoSOX and BODIPY 581/591 C11. Results 5 mitochondrial oxidative stress-related genes (CTSL, TXNRD2, NUDT1, STOX1, CYP2E1) were screened by differential expression analysis and Cox analysis and incorporated in a risk model which yielded a strong prediction accuracy (AUC value = 0.967). Furthermore, this model was strongly related to immune cell infiltration and mutation status and could identify potential targeted therapeutic drugs for GBM. Finally, we selected NUDT1 for further validation in vitro. The results showed that NUDT1 was elevated in GBM, and knockdown of NUDT1 inhibited the proliferation and induced apoptosis of GBM cells, while knockdown of NUDT1 damaged mitochondrial homeostasis and induced oxidative stress in GBM cells. Conclusion Our study was the first to propose a prognostic model of mitochondria and oxidative stress-related genes, which provided potential therapeutic strategies for GBM patients.

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Pan-Cancer Analysis Reveals SH3TC2 as an Oncogene for Colorectal Cancer and Promotes Tumorigenesis via the MAPK Pathway

Cited by 13 publications

References 61 publications

Dihydroartemisinin Enhances the Effects of Oxaliplatin by Activating PDCD5/ARAF mediated Signal Transduction in Colon Cancer

Dihydroartemisinin Enhances the Effects of Oxaliplatin by Activating PDCD5/ARAF mediated Signal Transduction in Colon Cancer

Hypoxia-Inducible Factor-2-Altered Urothelial Carcinoma: Clinical and Genomic Features

Identification and validation of a novel prognostic signature based on mitochondria and oxidative stress related genes for glioblastoma

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