title: Silencing of high-mobility group box 2 (HMGB2) modulates cisplatin and 5-fluorouracil sensitivity in head and neck squamous cell carcinoma.
abstract: Dysregulation of protein expression is associated with most diseases including cancer. MS-based proteomic analysis is widely employed as a tool to study protein dysregulation in cancers. Proteins that are differentially expressed in head and neck squamous cell carcinoma (HNSCC) cell lines compared to the normal oral cell line could serve as biomarkers for patient stratification. To understand the proteomic complexity in HNSCC, we carried out iTRAQ-based MS analysis on a panel of HNSCC cell lines in addition to a normal oral keratinocyte cell line. LC-MS/MS analysis of total proteome of the HNSCC cell lines led to the identification of 3263 proteins, of which 185 proteins were overexpressed and 190 proteins were downregulated more than twofold in at least two of the three HNSCC cell lines studied. Among the overexpressed proteins, 23 proteins were related to DNA replication and repair. These included high-mobility group box 2 (HMGB2) protein, which was overexpressed in all three HNSCC lines studied. Overexpression of HMGB2 has been reported in various cancers, yet its role in HNSCC remains unclear. Immunohistochemical labeling of HMGB2 in a panel of HNSCC tumors using tissue microarrays revealed overexpression in 77% (54 of 70) of tumors. The HMGB proteins are known to bind to DNA structure resulting from cisplatin-DNA adducts and affect the chemosensitivity of cells. We observed that siRNA-mediated silencing of HMGB2 increased the sensitivity of the HNSCC cell lines to cisplatin and 5-FU. We hypothesize that targeting HMGB2 could enhance the efficacy of existing chemotherapeutic regimens for treatment of HNSCC. All MS data have been deposited in the ProteomeXchange with identifier PXD000737 (http://proteomecentral.proteomexchange.org/dataset/PXD000737).
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore, India; Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, India.
authors.forename: Nazia
authors.initials: N
authors.lastname: Syed
authors.forename: Sandip
authors.initials: S
authors.lastname: Chavan
authors.forename: Nandini A
authors.initials: NA
authors.lastname: Sahasrabuddhe
authors.forename: Santosh
authors.initials: S
authors.lastname: Renuse
authors.forename: Gajanan
authors.initials: G
authors.lastname: Sathe
authors.forename: Vishalakshi
authors.initials: V
authors.lastname: Nanjappa
authors.forename: Aneesha
authors.initials: A
authors.lastname: Radhakrishnan
authors.forename: Remya
authors.initials: R
authors.lastname: Raja
authors.forename: Sneha M
authors.initials: SM
authors.lastname: Pinto
authors.forename: Anand
authors.initials: A
authors.lastname: Srinivasan
authors.forename: T S Keshava
authors.initials: TS
authors.lastname: Prasad
authors.forename: Kotteazeth
authors.initials: K
authors.lastname: Srikumar
authors.forename: Harsha
authors.initials: H
authors.lastname: Gowda
authors.forename: Vani
authors.initials: V
authors.lastname: Santosh
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey
authors.forename: Aditi
authors.initials: A
authors.lastname: Chatterjee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology*; D024261:HMGB2 Protein / Q000032:analysis / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D040901:Proteomics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D053719:Tandem Mass Spectrometry
chemical_list: D000970:Antineoplastic Agents; D024261:HMGB2 Protein; D034741:RNA, Small Interfering; D002945:Cisplatin; D005472:Fluorouracil
keywords: Antimetabolite; Biomarker; Biomedicine; Drug resistance; In vitro labeling