Lysine 2-hydroxyisobutyrylation proteomics reveals protein modification alteration in the actin cytoskeleton pathway of oral squamous cell carcinoma

Zhang, Zeyu1,2; Xie, Hongliang1; Zuo, Wenxin1; Tang, Jianming1; Zeng, Zhipeng1; Cai, Wanxia1; Lai, Liusheng3; Lu, Yongpin2; Shen, Lingjun2; Dong, Xiangnan2; Yin, Lianghong2; Tang, Donge1; Dai, Yong1,3

2021-10-30

10.1016/j.jprot.2021.104371

Journal of Proteomics   影响因子和分区

1874-3919

1876-7737

As the most commonplace malignant carcinoma in the oral cavity, oral squamous cell carcinoma (OSCC) is highly invasive and prone to recurrence. The nosogenesis of OSCC are affected by epigenetics. Recently, a newly-found post-translational modification of lysine, 2-hydroxyisobutylation (Khib), has been proved to play a critical role in biological regulation. However, no research has evaluated the mechanism of Khib in oral cancer. Here, we performed liquid chromatography-mass spectrometry-based quantitative proteomics combined with bioinformatics analysis to reveal and evaluate Khib protein alterations in OSCC. Numerous proteins in OSCC undergo up regulated modification of Khib. We quantified and identified 967 proteins with differential expression levels, and 617 2-hydroxyisobutylated proteins with 938 Khib sites. Among them, 125 proteins both differentially expressed and accompanied by obvious Khib modification were further identified and analyzed through KEGG-based and ingenuity pathway analysis (IPA). These proteins are enriched in the actin cytoskeleton regulatory pathway, and IPA predicted that they alter the state of actin aggregation and stability, hence impacting and regulating the actin cytoskeleton in OSCC. This is the first 2-hydroxyisobutylated modification proteomics performed for OSCC. Khib protein is significantly concentrated in the actin cytoskeleton regulatory pathway, indicating that this pathway may mediate the tumorigenesis or exacerbation of OSCC. Significance: This is the first study that revealed the alterations of Khib protein in oral squamous cell carcinoma through LC-MS/MS-based modified proteomic. Our data showed that the protein in the actin cytoskeleton regulatory pathway was underwent significant Khib modification and abundance changes. We applied predictive function in IPA software to analyze and clarify that the aggregation of actin and the regulation of actin stability that mediated by the actin cytoskeleton regulatory pathway may be the potential mechanism of the occurrence and development of oral squamous cell carcinoma. Our research broadens the understanding of the pathogenesis of oral squamous cell carcinoma and provides new insights for future research.

Oral squamous cell carcinoma Lysine 2-hydroxyisobutyrylation Post-translational modifications Actin cytoskeleton Mass spectrometry

SCI

英语

第一 ; 通讯

science and technology plan of Shenzhen[JCYJ20180306140810282] ; Guangxi Key Laboratory of Metabolic Diseases Research[20-065-76] ; Natural Science Foundation of Guangxi[2017GXNSFAA198185]

Biochemistry & Molecular Biology

Biochemical Research Methods

WOS:000696501000004

ELSEVIER

Web of Science

1.Jinan Univ, Southern Univ Sci & Technol, Affiliated Hosp 1, Clin Med Coll 2,Shenzhen Peoples Hosp, CN-518020 Shenzhen 518020, Peoples R China
2.Jinan Univ, Affiliated Hosp 1, Dept Nephrol & Blood Purificat, Guangzhou 510632, Peoples R China
3.Southern Med Univ, Affiliated Hosp 924, Guangxi Key Lab Metab Dis Res, Guilin 541002, Guangxi, Peoples R China

Zhang, Zeyu,Xie, Hongliang,Zuo, Wenxin,et al. Lysine 2-hydroxyisobutyrylation proteomics reveals protein modification alteration in the actin cytoskeleton pathway of oral squamous cell carcinoma[J]. Journal of Proteomics,2021,249.

Zhang, Zeyu.,Xie, Hongliang.,Zuo, Wenxin.,Tang, Jianming.,Zeng, Zhipeng.,...&Dai, Yong.(2021).Lysine 2-hydroxyisobutyrylation proteomics reveals protein modification alteration in the actin cytoskeleton pathway of oral squamous cell carcinoma.Journal of Proteomics,249.

Zhang, Zeyu,et al."Lysine 2-hydroxyisobutyrylation proteomics reveals protein modification alteration in the actin cytoskeleton pathway of oral squamous cell carcinoma".Journal of Proteomics 249(2021).