scholarly journals Relevance of BRAF Subcellular Localization and Its Interaction with KRAS and KIT Mutations in Skin Melanoma

2021 ◽  
Vol 22 (21) ◽  
pp. 11918
Author(s):  
Marius-Alexandru Beleaua ◽  
Ioan Jung ◽  
Cornelia Braicu ◽  
Doina Milutin ◽  
Simona Gurzu

Although skin melanoma (SKM) represents only one-quarter of newly diagnosed skin malignant tumors, it presents a high mortality rate. Hence, new prognostic and therapeutic tools need to be developed. This study focused on investigating the prognostic value of the subcellular expression of BRAF, KRAS, and KIT in SKM in correlation with their gene-encoding interactions. In silico analysis of the abovementioned gene interactions, along with their mRNA expression, was conducted, and the results were validated at the protein level using immunohistochemical (IHC) stains. For IHC expression, the encoded protein expressions were checked on 96 consecutive SKMs and 30 nevi. The UALCAN database showed no prognostic value for the mRNA expression level of KRAS and BRAF and demonstrated a longer survival for patients with low mRNA expression of KIT in SKMs. IHC examinations of SKMs confirmed the UALCAN data and showed that KIT expression was inversely correlated with ulceration, Breslow index, mitotic rate, and pT stage. KRAS expression was also found to be inversely correlated with ulceration and perineural invasion. When the subcellular expression of BRAF protein was recorded (nuclear vs. cytoplasmatic vs. mixed nucleus + cytoplasm), a direct correlation was emphasized between nuclear positivity and lymphovascular or perineural invasion. The independent prognostic value was demonstrated for mixed expression of the BRAF protein in SKM. BRAF cytoplasmic predominance, in association with KIT’s IHC positivity, was more frequently observed in early-stage nonulcerated SKMs, which displayed a low mitotic rate and a late death event. The present study firstly verified the possible prognostic value of BRAF subcellular localization in SKMs. A low mRNA expression or IHC cytoplasmic positivity for KIT and BRAF might be used as a positive prognostic parameter of SKM. SKM’s BRAF nuclear positivity needs to be evaluated in further studies as a possible indicator of perineural and lymphovascular invasion.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Guson Boonyoung ◽  
Tanate Panrat ◽  
Amornrat Phongdara ◽  
Warapond Wanna

AbstractThe 14-3-3 proteins interact with a wide variety of cellular proteins for many diverse functions in biological processes. In this study, a yeast two-hybrid assay revealed that two 14-3-3ε isoforms (14-3-3ES and 14-3-3EL) interacted with Rab11 in the white shrimp Litopenaeus vannamei (LvRab11). The interaction of 14-3-3ε and LvRab11 was confirmed by a GST pull-down assay. The LvRab11 open reading frame was 645 bp long, encoding a protein of 214 amino acids. Possible complexes of 14-3-3ε isoforms and LvRab11 were elucidated by in silico analysis, in which LvRab11 showed a better binding energy score with 14-3-3EL than with 14-3-3ES. In shrimp challenged with the white spot syndrome virus (WSSV), the mRNA expression levels of LvRab11 and 14-3-3ε were significantly upregulated at 48 h after challenge. To determine whether LvRab11 and binding between 14-3-3ε and LvRab11 are active against WSSV infection, an in vivo neutralization assay and RNA interference were performed. The results of in vivo neutralization showed that LvRab11 and complexes of 14-3-3ε/LvRab11 delayed mortality in shrimp challenged with WSSV. Interestingly, in the RNAi experiments, the silencing effect of LvRab11 in WSSV-infected shrimp resulted in decreased ie-1 mRNA expression and WSSV copy number. Whereas suppression of complex 14-3-3ε/LvRab11 increased WSSV replication. This study has suggested two functions of LvRab11 in shrimp innate immunity; (1) at the early stage of WSSV infection, LvRab11 might play an important role in WSSV infection processes and (2) at the late stage of infection, the 14-3-3ε/LvRab11 interaction acquires functions that are involved in immune response against WSSV invasion.


2019 ◽  
Vol 8 (15) ◽  
pp. 6487-6502
Author(s):  
Quanfa Han ◽  
Chuangye Han ◽  
Xiwen Liao ◽  
Ketuan Huang ◽  
Xiangkun Wang ◽  
...  

2018 ◽  
Vol 7 (10) ◽  
pp. 5066-5082 ◽  
Author(s):  
Marinos Tsiatas ◽  
Konstantine T. Kalogeras ◽  
Kyriaki Manousou ◽  
Ralph M. Wirtz ◽  
Helen Gogas ◽  
...  

2021 ◽  
Author(s):  
Peixin Lu ◽  
Jinying Jiang ◽  
Jun Lu

Abstract Background: Gastric cancer (GC) is one of the most common malignant tumors worldwide with a high incidence and mortality, making it urgent to search for potential biomarkers to improve the prognosis of patients. Integrin β (ITGB) superfamily members have been reported to participate in the biological process in various tumors. However, the expression and prognostic value of ITGBs in GC have not been clarified. In this study, the expression and roles of ITGBs in stomach adenocarcinoma (STAD) were investigated with ONCOMINE, UALCAN, The Human Protein Atlas, GEPIA, Kaplan-Meier Plotter, NetworkAnalyst, cBioPortal, STRING, GeneMANIA, David 6.8 and TIMER. Results: The transcriptional levels of ITGB1, 2, 4, 5, 6 and 8, and the protein expression of ITGB4, 5, 6 and 8 were significantly elevated while the transcriptional level of ITGB7 was significantly reduced in GC. High mRNA expression of ITGB1, 3 and 5, and low mRNA expression of ITGB4 were associated with short overall survival (OS), and high mRNA expression of ITGB6 was associated with short disease-free survival (DFS) in STAD patients. We also identified DAB2 as the potential transcription factor for ITGB3 and ITGB5, and TFAP2A for ITGB4 in STAD. Moreover, the functions of ITGB superfamily members were primarily related to regulation of actin cytoskeleton, focal adhesion and PI3K-Akt signalling pathway. The expression of ITGBs was significantly correlated with the infiltration of diverse immune cells, B cell, CD8+ T cell, CD4+ T cell, macrophage, neutrophil and dendritic cell.Conclusion: Taken together, our study indicated that ITGB superfamily members could be a potential prognostic target in the development of anti-STAD therapeutics. However, further experimental studies are still necessary to elucidate the mechanism of ITGBs.


2019 ◽  
Vol 20 (20) ◽  
pp. 5177
Author(s):  
Ishiyama ◽  
Tamura ◽  
Ito ◽  
Takei ◽  
Hoshi ◽  
...  

The deletion of Mecp2, the gene encoding methyl-CpG-binding protein 2, causes severe breathing defects and developmental anomalies in mammals. In Mecp2-null mice, impaired GABAergic neurotransmission is demonstrated at the early stage of life. GABAergic dysfunction in neurons in the rostral ventrolateral medulla (RVLM) is considered as a primary cause of breathing abnormality in Mecp2-null mice, but its molecular mechanism is unclear. Here, we report that mRNA expression levels of Gad1, which encodes glutamate decarboxylase 67 (GAD67), in the RVLM of Mecp2-null (Mecp2-/y, B6.129P2(C)-Mecp2tm1.1Bird/J) mice is closely related to the methylation status of its promoter, and valproate (VPA) can upregulate transcription from Gad1 through epigenetic mechanisms. The administration of VPA (300 mg/kg/day) together with L-carnitine (30 mg/kg/day) from day 8 to day 14 after birth increased Gad1 mRNA expression in the RVLM and reduced apnea counts in Mecp2-/y mice on postnatal day 15. Cytosine methylation levels in the Gad1 promoter were higher in the RVLM of Mecp2-/y mice compared to wild-type mice born to C57BL/6J females, while VPA treatment decreased the methylation levels in Mecp2-/y mice. Chromatin immunoprecipitation assay revealed that the VPA treatment reduced the binding of methyl-CpG binding domain protein 1 (MBD1) to the Gad1 promoter in Mecp2-/y mice. These results suggest that VPA improves breathing of Mecp2-/y mice by reducing the Gad1 promoter methylation, which potentially leads to the enhancement of GABAergic neurotransmission in the RVLM.


2017 ◽  
Vol 63 (5) ◽  
pp. 759-765
Author(s):  
Svetlana Kutukova ◽  
Natalya Belyak ◽  
Grigoriy Raskin ◽  
Marina Mukhina ◽  
Georgiy Manikhas ◽  
...  

The most frequent of malignant tumor cites of the oral mucosa are tongue - 55 %, mucosa of the cheek - 12 %, the fundus of the oral cavity - 10 %, the alveolar process of the upper jaw and the hard palate - 9 %, the alveolar process of the lower jaw - 6 %, the soft palate - 2 %. Malignant tumor cells carry PD-L1 ligands on their surface and its expression level is often correlated with an unfavorable prognosis in particular for such tumors as melanoma, kidney cancer and non-small cell lung cancer. It is relevant to evaluate the correlation between overexpression of PD-L1 and overall survival in patients with malignant tumors of the oral mucosa.


Author(s):  
Amrita Naik ◽  
Damodar Reddy Edla

Lung cancer is the most common cancer throughout the world and identification of malignant tumors at an early stage is needed for diagnosis and treatment of patient thus avoiding the progression to a later stage. In recent times, deep learning architectures such as CNN have shown promising results in effectively identifying malignant tumors in CT scans. In this paper, we combine the CNN features with texture features such as Haralick and Gray level run length matrix features to gather benefits of high level and spatial features extracted from the lung nodules to improve the accuracy of classification. These features are further classified using SVM classifier instead of softmax classifier in order to reduce the overfitting problem. Our model was validated on LUNA dataset and achieved an accuracy of 93.53%, sensitivity of 86.62%, the specificity of 96.55%, and positive predictive value of 94.02%.


BMC Genomics ◽  
2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Wenjing Tao ◽  
Lina Sun ◽  
Hongjuan Shi ◽  
Yunying Cheng ◽  
Dongneng Jiang ◽  
...  

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