Tip110/SART3 regulates IL-8 expression and predicts the clinical outcomes in melanoma

Khalid A. Timani, Balázs Gyorffy, Ying Liu, Khalid S. Mohammad, Johnny Jianglin He

Research output: Contribution to journalLetterResearchpeer-review

Abstract

Tip110, an important regulator of several oncogenic proteins, was significantly downregulated in human metastatic melanoma cells exposed to a hypoxic condition. Therefore, in this study, we set to determine whether differential expression of Tip110 could be an important indicator for melanoma tumorigenesis and metastasis. We found that in melanoma, but not in other cancer types, Tip110 knockdown enhanced significant expression and secretion of IL-8 and melanoma cells invasions. This induction was further potentiated under hypoxia and by inflammatory cytokine and found independent of TNF-α autocrine signaling. We further showed that Tip110 knockdown-mediated IL-8 induction involved IL-8 mRNA stability. Furthermore, the transcriptomic profiling data and survival from 455 melanoma patients demonstrated that the correlation between Tip110 expression and the clinical outcomes in melanoma was stage-dependent. These findings uncover important roles of Tip110 in melanoma tumorigenesis and metastasis through regulation of IL-8 and hope to provide new clues for future therapeutic strategies.

Original languageEnglish
Article number124
JournalMolecular Cancer
Volume17
Issue number1
DOIs
StatePublished - 17 Aug 2018

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Interleukin-8
Melanoma
Carcinogenesis
Autocrine Communication
Neoplasm Metastasis
RNA Stability
Down-Regulation
Cytokines
Survival
Neoplasms
Proteins

Keywords

  • Hypoxia
  • IL-8
  • Melanoma
  • TP53, NF-ΚB
  • Tip110/SART3

Cite this

@article{574501477e324b468e3702860bef79b7,
title = "Tip110/SART3 regulates IL-8 expression and predicts the clinical outcomes in melanoma",
abstract = "Tip110, an important regulator of several oncogenic proteins, was significantly downregulated in human metastatic melanoma cells exposed to a hypoxic condition. Therefore, in this study, we set to determine whether differential expression of Tip110 could be an important indicator for melanoma tumorigenesis and metastasis. We found that in melanoma, but not in other cancer types, Tip110 knockdown enhanced significant expression and secretion of IL-8 and melanoma cells invasions. This induction was further potentiated under hypoxia and by inflammatory cytokine and found independent of TNF-α autocrine signaling. We further showed that Tip110 knockdown-mediated IL-8 induction involved IL-8 mRNA stability. Furthermore, the transcriptomic profiling data and survival from 455 melanoma patients demonstrated that the correlation between Tip110 expression and the clinical outcomes in melanoma was stage-dependent. These findings uncover important roles of Tip110 in melanoma tumorigenesis and metastasis through regulation of IL-8 and hope to provide new clues for future therapeutic strategies.",
keywords = "Hypoxia, IL-8, Melanoma, TP53, NF-ΚB, Tip110/SART3",
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year = "2018",
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journal = "Molecular Cancer",
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Tip110/SART3 regulates IL-8 expression and predicts the clinical outcomes in melanoma. / Timani, Khalid A.; Gyorffy, Balázs; Liu, Ying; Mohammad, Khalid S.; He, Johnny Jianglin.

In: Molecular Cancer, Vol. 17, No. 1, 124, 17.08.2018.

Research output: Contribution to journalLetterResearchpeer-review

TY - JOUR

T1 - Tip110/SART3 regulates IL-8 expression and predicts the clinical outcomes in melanoma

AU - Timani, Khalid A.

AU - Gyorffy, Balázs

AU - Liu, Ying

AU - Mohammad, Khalid S.

AU - He, Johnny Jianglin

PY - 2018/8/17

Y1 - 2018/8/17

N2 - Tip110, an important regulator of several oncogenic proteins, was significantly downregulated in human metastatic melanoma cells exposed to a hypoxic condition. Therefore, in this study, we set to determine whether differential expression of Tip110 could be an important indicator for melanoma tumorigenesis and metastasis. We found that in melanoma, but not in other cancer types, Tip110 knockdown enhanced significant expression and secretion of IL-8 and melanoma cells invasions. This induction was further potentiated under hypoxia and by inflammatory cytokine and found independent of TNF-α autocrine signaling. We further showed that Tip110 knockdown-mediated IL-8 induction involved IL-8 mRNA stability. Furthermore, the transcriptomic profiling data and survival from 455 melanoma patients demonstrated that the correlation between Tip110 expression and the clinical outcomes in melanoma was stage-dependent. These findings uncover important roles of Tip110 in melanoma tumorigenesis and metastasis through regulation of IL-8 and hope to provide new clues for future therapeutic strategies.

AB - Tip110, an important regulator of several oncogenic proteins, was significantly downregulated in human metastatic melanoma cells exposed to a hypoxic condition. Therefore, in this study, we set to determine whether differential expression of Tip110 could be an important indicator for melanoma tumorigenesis and metastasis. We found that in melanoma, but not in other cancer types, Tip110 knockdown enhanced significant expression and secretion of IL-8 and melanoma cells invasions. This induction was further potentiated under hypoxia and by inflammatory cytokine and found independent of TNF-α autocrine signaling. We further showed that Tip110 knockdown-mediated IL-8 induction involved IL-8 mRNA stability. Furthermore, the transcriptomic profiling data and survival from 455 melanoma patients demonstrated that the correlation between Tip110 expression and the clinical outcomes in melanoma was stage-dependent. These findings uncover important roles of Tip110 in melanoma tumorigenesis and metastasis through regulation of IL-8 and hope to provide new clues for future therapeutic strategies.

KW - Hypoxia

KW - IL-8

KW - Melanoma

KW - TP53, NF-ΚB

KW - Tip110/SART3

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U2 - 10.1186/s12943-018-0868-z

DO - 10.1186/s12943-018-0868-z

M3 - Letter

VL - 17

JO - Molecular Cancer

JF - Molecular Cancer

SN - 1476-4598

IS - 1

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ER -