Histone demethylase JARID1B/KDM5B promotes aggressiveness of non-small cell lung cancer and serves as a good prognostic predictor

Kuang Tai Kuo, Wen Chien Huang, Oluwaseun Adebayo Bamodu, Wei Hwa Lee, Chun Hua Wang, M. Hsiao, Liang Shun Wang, Chi Tai Yeh

研究成果: 雜誌貢獻文章

6 引文 (Scopus)

摘要

Background: Lung cancer is the leading cause of cancer death worldwide. Recently, epigenetic dysregulation has been known to promote tumor progression and therefore may be a therapeutic target for anticancer therapy. JARID1B, a member of histone demethylases, has been found to be related to tumorigenesis in certain kinds of cancers. However, its biological roles in non-small cell lung cancer (NSCLC) remain largely unclear. Methods: We firstly examined the expression of JARID1B in surgical specimens and six NSCLC cell lines. Then, we evaluated the relationship between JARID1B expression and clinicopathologic parameters in 72 NSCLC patients, thereby established its prognostic importance. We subsequently studied the functional roles of JARID1B in tumorigenesis to verify its clinicopathologic significance. Results: Our results showed that JARID1B was overexpressed in NSCLC cells and JARID1B overexpression was associated with tumor size, lymph node metastasis, advanced stages, and poor overall survival in NSCLC patients. JARID1B overexpression resulted in increased cell proliferation and formation of tumorspheres and correlated positively with the expression of cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) markers, while the c-Met signaling pathway was actively involved. It also correlated with the strength of resistance to cisplatin and doxorubicin. On the contrary, downregulation of JARID1B expression by applying shRNA or JARID1B inhibitor PBIT reversed these phenomena. Conclusions: JARID1B worsens prognosis of NSCLC patients by promotion of tumor aggressiveness through multiple biological facets which were associated with activation of the c-Met signaling, and can be a novel prognostic biomarker and therapeutic target for NSCLC.
原文英語
文章編號107
期刊Clinical Epigenetics
10
發行號1
DOIs
出版狀態已發佈 - 八月 9 2018

指紋

Histone Demethylases
Non-Small Cell Lung Carcinoma
Neoplasms
Carcinogenesis
Epithelial-Mesenchymal Transition
Neoplastic Stem Cells
Epigenomics
Doxorubicin
Small Interfering RNA
Cisplatin
Cause of Death
Lung Neoplasms
Therapeutics
Down-Regulation
Biomarkers
Lymph Nodes
Cell Proliferation
Neoplasm Metastasis
Cell Line
Survival

Keywords

  • C-Met
  • Cancer stem cells
  • JARID1B
  • Lung cancer
  • Prognosis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Developmental Biology
  • Genetics(clinical)

引用此文

@article{bceb7dc88fc5462abf133363d4a08232,
title = "Histone demethylase JARID1B/KDM5B promotes aggressiveness of non-small cell lung cancer and serves as a good prognostic predictor",
abstract = "Background: Lung cancer is the leading cause of cancer death worldwide. Recently, epigenetic dysregulation has been known to promote tumor progression and therefore may be a therapeutic target for anticancer therapy. JARID1B, a member of histone demethylases, has been found to be related to tumorigenesis in certain kinds of cancers. However, its biological roles in non-small cell lung cancer (NSCLC) remain largely unclear. Methods: We firstly examined the expression of JARID1B in surgical specimens and six NSCLC cell lines. Then, we evaluated the relationship between JARID1B expression and clinicopathologic parameters in 72 NSCLC patients, thereby established its prognostic importance. We subsequently studied the functional roles of JARID1B in tumorigenesis to verify its clinicopathologic significance. Results: Our results showed that JARID1B was overexpressed in NSCLC cells and JARID1B overexpression was associated with tumor size, lymph node metastasis, advanced stages, and poor overall survival in NSCLC patients. JARID1B overexpression resulted in increased cell proliferation and formation of tumorspheres and correlated positively with the expression of cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) markers, while the c-Met signaling pathway was actively involved. It also correlated with the strength of resistance to cisplatin and doxorubicin. On the contrary, downregulation of JARID1B expression by applying shRNA or JARID1B inhibitor PBIT reversed these phenomena. Conclusions: JARID1B worsens prognosis of NSCLC patients by promotion of tumor aggressiveness through multiple biological facets which were associated with activation of the c-Met signaling, and can be a novel prognostic biomarker and therapeutic target for NSCLC.",
keywords = "C-Met, Cancer stem cells, JARID1B, Lung cancer, Prognosis, C-Met, Cancer stem cells, JARID1B, Lung cancer, Prognosis",
author = "Kuo, {Kuang Tai} and Huang, {Wen Chien} and Bamodu, {Oluwaseun Adebayo} and Lee, {Wei Hwa} and Wang, {Chun Hua} and M. Hsiao and Wang, {Liang Shun} and Yeh, {Chi Tai}",
year = "2018",
month = "8",
day = "9",
doi = "10.1186/s13148-018-0533-9",
language = "English",
volume = "10",
journal = "Clinical Epigenetics",
issn = "1868-7075",
publisher = "Springer Verlag",
number = "1",

}

TY - JOUR

T1 - Histone demethylase JARID1B/KDM5B promotes aggressiveness of non-small cell lung cancer and serves as a good prognostic predictor

AU - Kuo, Kuang Tai

AU - Huang, Wen Chien

AU - Bamodu, Oluwaseun Adebayo

AU - Lee, Wei Hwa

AU - Wang, Chun Hua

AU - Hsiao, M.

AU - Wang, Liang Shun

AU - Yeh, Chi Tai

PY - 2018/8/9

Y1 - 2018/8/9

N2 - Background: Lung cancer is the leading cause of cancer death worldwide. Recently, epigenetic dysregulation has been known to promote tumor progression and therefore may be a therapeutic target for anticancer therapy. JARID1B, a member of histone demethylases, has been found to be related to tumorigenesis in certain kinds of cancers. However, its biological roles in non-small cell lung cancer (NSCLC) remain largely unclear. Methods: We firstly examined the expression of JARID1B in surgical specimens and six NSCLC cell lines. Then, we evaluated the relationship between JARID1B expression and clinicopathologic parameters in 72 NSCLC patients, thereby established its prognostic importance. We subsequently studied the functional roles of JARID1B in tumorigenesis to verify its clinicopathologic significance. Results: Our results showed that JARID1B was overexpressed in NSCLC cells and JARID1B overexpression was associated with tumor size, lymph node metastasis, advanced stages, and poor overall survival in NSCLC patients. JARID1B overexpression resulted in increased cell proliferation and formation of tumorspheres and correlated positively with the expression of cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) markers, while the c-Met signaling pathway was actively involved. It also correlated with the strength of resistance to cisplatin and doxorubicin. On the contrary, downregulation of JARID1B expression by applying shRNA or JARID1B inhibitor PBIT reversed these phenomena. Conclusions: JARID1B worsens prognosis of NSCLC patients by promotion of tumor aggressiveness through multiple biological facets which were associated with activation of the c-Met signaling, and can be a novel prognostic biomarker and therapeutic target for NSCLC.

AB - Background: Lung cancer is the leading cause of cancer death worldwide. Recently, epigenetic dysregulation has been known to promote tumor progression and therefore may be a therapeutic target for anticancer therapy. JARID1B, a member of histone demethylases, has been found to be related to tumorigenesis in certain kinds of cancers. However, its biological roles in non-small cell lung cancer (NSCLC) remain largely unclear. Methods: We firstly examined the expression of JARID1B in surgical specimens and six NSCLC cell lines. Then, we evaluated the relationship between JARID1B expression and clinicopathologic parameters in 72 NSCLC patients, thereby established its prognostic importance. We subsequently studied the functional roles of JARID1B in tumorigenesis to verify its clinicopathologic significance. Results: Our results showed that JARID1B was overexpressed in NSCLC cells and JARID1B overexpression was associated with tumor size, lymph node metastasis, advanced stages, and poor overall survival in NSCLC patients. JARID1B overexpression resulted in increased cell proliferation and formation of tumorspheres and correlated positively with the expression of cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) markers, while the c-Met signaling pathway was actively involved. It also correlated with the strength of resistance to cisplatin and doxorubicin. On the contrary, downregulation of JARID1B expression by applying shRNA or JARID1B inhibitor PBIT reversed these phenomena. Conclusions: JARID1B worsens prognosis of NSCLC patients by promotion of tumor aggressiveness through multiple biological facets which were associated with activation of the c-Met signaling, and can be a novel prognostic biomarker and therapeutic target for NSCLC.

KW - C-Met

KW - Cancer stem cells

KW - JARID1B

KW - Lung cancer

KW - Prognosis

KW - C-Met

KW - Cancer stem cells

KW - JARID1B

KW - Lung cancer

KW - Prognosis

UR - http://www.scopus.com/inward/record.url?scp=85054930378&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054930378&partnerID=8YFLogxK

U2 - 10.1186/s13148-018-0533-9

DO - 10.1186/s13148-018-0533-9

M3 - Article

AN - SCOPUS:85054930378

VL - 10

JO - Clinical Epigenetics

JF - Clinical Epigenetics

SN - 1868-7075

IS - 1

M1 - 107

ER -