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Chronic shisha exposure alters phosphoproteome of oral keratinocytes.
Journal of Cell Communication and Signaling ( IF 4.1 ) Pub Date : 2019-07-19 , DOI: 10.1007/s12079-019-00528-4
Shankargouda Patil 1, 2 , Pavithra Rajagopalan 3 , Krishna Patel 3 , Tejaswini Subbannayya 3 , Niraj Babu 3, 4 , Sonali V Mohan 3, 4, 5 , Jayshree Advani 3 , Gajanan Sathe 3 , Shilpa Bhandi 6 , Hitendra S Solanki 3 , David Sidransky 7 , Aditi Chatterjee 3, 4 , Harsha Gowda 3, 4 , Marco Ferrari 2, 8
Affiliation  

Shisha smoking has been epidemiologically linked to oral cancer. However, few studies have investigated the pathobiology of shisha-induced cellular transformation. We studied the effects of chronic shisha exposure (8 months) in an in vitro model using immortalized, non-neoplastic oral keratinocytes (OKF6/TERT1). Quantitative proteomic and phosphoproteomic analyses were performed on OKF6/TERT1 cells treated with shisha extract for a period of 8 months. Pathway analysis was carried out to identify significantly enriched biological processes in shisha-treated cells. Chronic shisha exposure resulted in increased cell scattering phenomenon in OKF6/TERT1 cells. Data analysis revealed differential phosphorylation of 164 peptides (fold change ≥1.5, p ≤ 0.0.5) corresponding to 136 proteins. Proteins associated with mTORC1 and EIF4F complexes involved in initiating protein translation were seen to be enriched upon shisha treatment. Network analysis also highlighted downregulation of proteins involved in Type I interferon signaling in shisha-treated cells. Quantitative phosphoproteomic approach elucidated global perturbations to the molecular milieu of oral keratinocytes upon shisha exposure. Further studies are needed to validate putative targets in oral cancer patients with shisha smoking history.

中文翻译:

慢性水烟暴露会改变口腔角质形成细胞的磷酸化蛋白质组。

水烟的流行病学与口腔癌有关。然而,很少有研究调查水烟诱导的细胞转化的病理生物学。我们在永生化,非肿瘤性口腔角质形成细胞(OKF6 / TERT1)的体外模型中研究了慢性水烟暴露(8个月)的影响。对用水烟提取物处理8个月的OKF6 / TERT1细胞进行了蛋白质组学和磷酸化蛋白质组学定量分析。进行途径分析以鉴定水烟处理过的细胞中明显富集的生物学过程。长期接触水烟导致OKF6 / TERT1细胞中的细胞散射现象增加。数据分析揭示了164种肽的差异磷酸化(倍数变化≥1.5,p ≤0.0.5),相当于136种蛋白质。水烟处理后,发现与mTORC1和EIF4F复合体相关的蛋白质参与起始蛋白质翻译被富集。网络分析还强调了水烟处理过的细胞中与I型干扰素信号传导有关的蛋白质的下调。定量磷酸化蛋白质组学方法阐明了水烟暴露后对口腔角质形成细胞分子环境的整体扰动。需要进一步的研究来验证具有水烟吸烟史的口腔癌患者的推定目标。
更新日期:2019-07-19
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