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Establishment of a new OSCC cell line derived from OLK and identification of malignant transformation-related proteins by differential proteomics approach

机译:建立基于OLK的新型OSCC细胞系并通过差异蛋白质组学方法鉴定恶性转化相关蛋白

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摘要

Oral squamous cell carcinoma (OSCC) is usually preceded by the oral premalignant lesions, mainly oral leukoplakia (OLK) after repeated insults of carcinogens, tobacco. B(a)P and DMBA are key carcinogens in tobacco smoke. In the present study, for the first time we established the cancerous cell line OSCC-BD induced by B(a)P/DMBA mixture and transformed from dysplastic oral leukoplakia cell line DOK. Cell morphology, proliferation ability, migration ability, colony formation, and tumorigenicity were studied and confirmed the malignant characteristics of OSCC-BD cells. We further identified the differential proteins between DOK and OSCC-BD cells by stable isotope dimethyl labeling based quantitative proteomic method, which showed 18 proteins up-regulated and 16 proteins down-regulated with RSD < 8%. Differential proteins are mainly related to cell cycle, cell proliferation, DNA replication, RNA splicing and apoptosis. Abberant binding function, catalysis activity and transportor activity of differential proteins might contribute to the malignant transformation of OLK. Of the 34 identified differential proteins with RSD < 8%, 13 novel cancer-related proteins were reported in the present study. This study might provide a new insight into the mechanism of OLK malignant transformation and the potent biomarkers for early diagnosis, meanwhile further facilitate the application of the quantification proteomics to carcinogenesis research.
机译:口腔鳞状细胞癌(OSCC)通常先于口腔癌前病变,主要是经反复致癌物,烟草伤害的口腔白斑(OLK)。 B(a)P和DMBA是烟草烟雾中的关键致癌物。在本研究中,我们首次建立了由B(a)P / DMBA混合物诱导并从发育异常的口腔白斑细胞DOK转化的癌细胞系OSCC-BD。研究了细胞形态,增殖能力,迁移能力,集落形成和致瘤性,并证实了OSCC-BD细胞的恶性特征。通过基于稳定同位素二甲基标记的定量蛋白质组学方法,我们进一步鉴定了DOK和OSCC-BD细胞之间的差异蛋白,结果显示18种蛋白上调,而16种蛋白的RSD <8%。差异蛋白主要与细胞周期,细胞增殖,DNA复制,RNA剪接和凋亡有关。差异蛋白的异常结合功能,催化活性和转运蛋白活性可能有助于OLK的恶性转化。在本研究中,已鉴定出的34种RSD <8%的差异蛋白中,有13种与癌症相关的新蛋白。这项研究可能为OLK恶性转化的机制和早期诊断的有效生物标志物提供新的见解,同时进一步促进定量蛋白质组学在致癌研究中的应用。

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