Silencing of high-mobility group box 2 (HMGB2) modulates cisplatin and 5-fluorouracil sensitivity in head and neck squamous cell carcinoma

Nazia Syed, Sandip Chavan, Nandini A. Sahasrabuddhe, Santosh Renuse, Gajanan Sathe, Vishalakshi Nanjappa, Aneesha Radhakrishnan, Remya Raja, Sneha M. Pinto, Anand Srinivasan, T. S.Keshava Prasad, Kotteazeth Srikumar, Harsha Gowda, Vani Santosh, David Sidransky, Joseph A. Califano, Akhilesh Pandey, Aditi Chatterjee

Research output: Contribution to journalArticle

17 Citations (Scopus)

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).

Original languageEnglish (US)
Pages (from-to)383-393
Number of pages11
JournalProteomics
Volume15
Issue number2-3
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Fluorouracil
Cisplatin
Cells
Cell Line
Proteins
Neoplasms
Proteomics
Tumors
HMGB2 Protein
HMGB Proteins
Carcinoma, squamous cell of head and neck
Epithelial Cells
DNA
Biomarkers
Proteome
Microarrays
DNA Replication
Keratinocytes
DNA Repair
Labeling

Keywords

  • Antimetabolite
  • Biomarker
  • Biomedicine
  • Drug resistance
  • In vitro labeling

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Syed, N., Chavan, S., Sahasrabuddhe, N. A., Renuse, S., Sathe, G., Nanjappa, V., ... Chatterjee, A. (2015). Silencing of high-mobility group box 2 (HMGB2) modulates cisplatin and 5-fluorouracil sensitivity in head and neck squamous cell carcinoma. Proteomics, 15(2-3), 383-393. https://doi.org/10.1002/pmic.201400338

Silencing of high-mobility group box 2 (HMGB2) modulates cisplatin and 5-fluorouracil sensitivity in head and neck squamous cell carcinoma. / Syed, Nazia; Chavan, Sandip; Sahasrabuddhe, Nandini A.; Renuse, Santosh; Sathe, Gajanan; Nanjappa, Vishalakshi; Radhakrishnan, Aneesha; Raja, Remya; Pinto, Sneha M.; Srinivasan, Anand; Prasad, T. S.Keshava; Srikumar, Kotteazeth; Gowda, Harsha; Santosh, Vani; Sidransky, David; Califano, Joseph A.; Pandey, Akhilesh; Chatterjee, Aditi.

In: Proteomics, Vol. 15, No. 2-3, 01.01.2015, p. 383-393.

Research output: Contribution to journalArticle

Syed, N, Chavan, S, Sahasrabuddhe, NA, Renuse, S, Sathe, G, Nanjappa, V, Radhakrishnan, A, Raja, R, Pinto, SM, Srinivasan, A, Prasad, TSK, Srikumar, K, Gowda, H, Santosh, V, Sidransky, D, Califano, JA, Pandey, A & Chatterjee, A 2015, 'Silencing of high-mobility group box 2 (HMGB2) modulates cisplatin and 5-fluorouracil sensitivity in head and neck squamous cell carcinoma', Proteomics, vol. 15, no. 2-3, pp. 383-393. https://doi.org/10.1002/pmic.201400338
Syed, Nazia ; Chavan, Sandip ; Sahasrabuddhe, Nandini A. ; Renuse, Santosh ; Sathe, Gajanan ; Nanjappa, Vishalakshi ; Radhakrishnan, Aneesha ; Raja, Remya ; Pinto, Sneha M. ; Srinivasan, Anand ; Prasad, T. S.Keshava ; Srikumar, Kotteazeth ; Gowda, Harsha ; Santosh, Vani ; Sidransky, David ; Califano, Joseph A. ; Pandey, Akhilesh ; Chatterjee, Aditi. / Silencing of high-mobility group box 2 (HMGB2) modulates cisplatin and 5-fluorouracil sensitivity in head and neck squamous cell carcinoma. In: Proteomics. 2015 ; Vol. 15, No. 2-3. pp. 383-393.
@article{118c2c7b7a944d029552dea531a635cc,
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).",
keywords = "Antimetabolite, Biomarker, Biomedicine, Drug resistance, In vitro labeling",
author = "Nazia Syed and Sandip Chavan and Sahasrabuddhe, {Nandini A.} and Santosh Renuse and Gajanan Sathe and Vishalakshi Nanjappa and Aneesha Radhakrishnan and Remya Raja and Pinto, {Sneha M.} and Anand Srinivasan and Prasad, {T. S.Keshava} and Kotteazeth Srikumar and Harsha Gowda and Vani Santosh and David Sidransky and Califano, {Joseph A.} and Akhilesh Pandey and Aditi Chatterjee",
year = "2015",
month = "1",
day = "1",
doi = "10.1002/pmic.201400338",
language = "English (US)",
volume = "15",
pages = "383--393",
journal = "Proteomics",
issn = "1615-9853",
publisher = "Wiley-VCH Verlag",
number = "2-3",

}

TY - JOUR

T1 - Silencing of high-mobility group box 2 (HMGB2) modulates cisplatin and 5-fluorouracil sensitivity in head and neck squamous cell carcinoma

AU - Syed, Nazia

AU - Chavan, Sandip

AU - Sahasrabuddhe, Nandini A.

AU - Renuse, Santosh

AU - Sathe, Gajanan

AU - Nanjappa, Vishalakshi

AU - Radhakrishnan, Aneesha

AU - Raja, Remya

AU - Pinto, Sneha M.

AU - Srinivasan, Anand

AU - Prasad, T. S.Keshava

AU - Srikumar, Kotteazeth

AU - Gowda, Harsha

AU - Santosh, Vani

AU - Sidransky, David

AU - Califano, Joseph A.

AU - Pandey, Akhilesh

AU - Chatterjee, Aditi

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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).

AB - 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).

KW - Antimetabolite

KW - Biomarker

KW - Biomedicine

KW - Drug resistance

KW - In vitro labeling

UR - http://www.scopus.com/inward/record.url?scp=84921313925&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84921313925&partnerID=8YFLogxK

U2 - 10.1002/pmic.201400338

DO - 10.1002/pmic.201400338

M3 - Article

C2 - 25327479

AN - SCOPUS:84921313925

VL - 15

SP - 383

EP - 393

JO - Proteomics

JF - Proteomics

SN - 1615-9853

IS - 2-3

ER -