Abstract

Food and Drug Administration to treat patients with relapsed/refractory multiple myelomas. Previous studies have demonstrated that bortezomib inhibits tumor cell proliferation and induces apoptosis by blocking the nuclear factor (NF)-κ B pathway. However, the exact mechanism by which bortezomib induces cancer cell apoptosis is still not well understood. In this study, we found that bortezomib significantly inhibited cell proliferation in both human Burkitt's lymphoma CA46 and Daudi cells. Through proteomic analysis, we found that bortezomib treatment changed the expression of various proteins in distinct functional categories including unfolding protein response (UPS), RNA processing, protein targeting and biosynthesis, apoptosis, and signal transduction. Among the proteins with altered expression, hnRNP K, hnRNP H, Hsp90α, Grp78, and Hsp7C were common to both Daudi and CA46 cells. Interestingly, bortezomib treatment downregulated the expression of high-molecular-weight (HMw) hnRNP K and c-Myc but upregulated the expression of low-molecular-weight (LMw) hnRNP K. Moreover, cell proliferation was significantly correlated with high expression of HMw hnRNP K and c-Myc. HMw and LMw hnRNP K were identified as sumoylated and desumoylated hnRNP K, respectively. Using transient transfection, we found that sumoylated hnRNP K increased c-Myc expression at the translational level and contributed to cell proliferation, and that Lys422 of hnRNP K is the candidate sumoylated residue. Our results suggest that besides inhibiting the ubiquitinproteasome pathway, bortezomib may inhibit cell proliferation by downregulating sumoylated hnRNP K and c-Myc expression in Burkitt's lymphoma cells.

Original languageEnglish
Pages (from-to)25988-26001
Number of pages14
JournalOncotarget
Volume6
Issue number28
DOIs
Publication statusPublished - 2015

Fingerprint

Heterogeneous-Nuclear Ribonucleoprotein K
Burkitt Lymphoma
Down-Regulation
Cell Proliferation
Molecular Weight
Apoptosis
Heterogeneous-Nuclear Ribonucleoprotein Group F-H
Unfolded Protein Response
Bortezomib
Protein Biosynthesis
Protein Transport
United States Food and Drug Administration
Multiple Myeloma
Proteomics
Transfection
Signal Transduction
Neoplasms
Proteins

Keywords

  • Bortezomib
  • Burkitt's lymphoma
  • C-Myc
  • HnRNP K
  • Sumoylation

ASJC Scopus subject areas

  • Oncology

Cite this

Bortezomib inhibits Burkitt's lymphoma cell proliferation by downregulating sumoylated hnRNP K and c-Myc expression. / Suk, Fat Moon; Lin, Shyr Yi; Lin, Ren-Jye; Hsine, Yung Hsin; Liao, Yen Ju; Fang, Sheng Uei; Liang, Yu Chih.

In: Oncotarget, Vol. 6, No. 28, 2015, p. 25988-26001.

Research output: Contribution to journalArticle

Suk, Fat Moon ; Lin, Shyr Yi ; Lin, Ren-Jye ; Hsine, Yung Hsin ; Liao, Yen Ju ; Fang, Sheng Uei ; Liang, Yu Chih. / Bortezomib inhibits Burkitt's lymphoma cell proliferation by downregulating sumoylated hnRNP K and c-Myc expression. In: Oncotarget. 2015 ; Vol. 6, No. 28. pp. 25988-26001.
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abstract = "Food and Drug Administration to treat patients with relapsed/refractory multiple myelomas. Previous studies have demonstrated that bortezomib inhibits tumor cell proliferation and induces apoptosis by blocking the nuclear factor (NF)-κ B pathway. However, the exact mechanism by which bortezomib induces cancer cell apoptosis is still not well understood. In this study, we found that bortezomib significantly inhibited cell proliferation in both human Burkitt's lymphoma CA46 and Daudi cells. Through proteomic analysis, we found that bortezomib treatment changed the expression of various proteins in distinct functional categories including unfolding protein response (UPS), RNA processing, protein targeting and biosynthesis, apoptosis, and signal transduction. Among the proteins with altered expression, hnRNP K, hnRNP H, Hsp90α, Grp78, and Hsp7C were common to both Daudi and CA46 cells. Interestingly, bortezomib treatment downregulated the expression of high-molecular-weight (HMw) hnRNP K and c-Myc but upregulated the expression of low-molecular-weight (LMw) hnRNP K. Moreover, cell proliferation was significantly correlated with high expression of HMw hnRNP K and c-Myc. HMw and LMw hnRNP K were identified as sumoylated and desumoylated hnRNP K, respectively. Using transient transfection, we found that sumoylated hnRNP K increased c-Myc expression at the translational level and contributed to cell proliferation, and that Lys422 of hnRNP K is the candidate sumoylated residue. Our results suggest that besides inhibiting the ubiquitinproteasome pathway, bortezomib may inhibit cell proliferation by downregulating sumoylated hnRNP K and c-Myc expression in Burkitt's lymphoma cells.",
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AU - Lin, Shyr Yi

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AU - Hsine, Yung Hsin

AU - Liao, Yen Ju

AU - Fang, Sheng Uei

AU - Liang, Yu Chih

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AB - Food and Drug Administration to treat patients with relapsed/refractory multiple myelomas. Previous studies have demonstrated that bortezomib inhibits tumor cell proliferation and induces apoptosis by blocking the nuclear factor (NF)-κ B pathway. However, the exact mechanism by which bortezomib induces cancer cell apoptosis is still not well understood. In this study, we found that bortezomib significantly inhibited cell proliferation in both human Burkitt's lymphoma CA46 and Daudi cells. Through proteomic analysis, we found that bortezomib treatment changed the expression of various proteins in distinct functional categories including unfolding protein response (UPS), RNA processing, protein targeting and biosynthesis, apoptosis, and signal transduction. Among the proteins with altered expression, hnRNP K, hnRNP H, Hsp90α, Grp78, and Hsp7C were common to both Daudi and CA46 cells. Interestingly, bortezomib treatment downregulated the expression of high-molecular-weight (HMw) hnRNP K and c-Myc but upregulated the expression of low-molecular-weight (LMw) hnRNP K. Moreover, cell proliferation was significantly correlated with high expression of HMw hnRNP K and c-Myc. HMw and LMw hnRNP K were identified as sumoylated and desumoylated hnRNP K, respectively. Using transient transfection, we found that sumoylated hnRNP K increased c-Myc expression at the translational level and contributed to cell proliferation, and that Lys422 of hnRNP K is the candidate sumoylated residue. Our results suggest that besides inhibiting the ubiquitinproteasome pathway, bortezomib may inhibit cell proliferation by downregulating sumoylated hnRNP K and c-Myc expression in Burkitt's lymphoma cells.

KW - Bortezomib

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