BPTF promotes hepatocellular carcinoma growth by modulating hTERT signaling and cancer stem cell traits

Xinrui Zhao, Fufu Zheng, Yizhuo Li, Jiaojiao Hao, Zhipeng Tang, Chunfang Tian, Qian Yang, Tianhua Zhu, Chaoliang Diao, Changlin Zhang, Manyu Chen, Sheng Hu, Ping Guo, Lizhi Zhang, Yina Liao, Wendan Yu, Miao Chen, Lijuan Zou, Wei Guo, Wu-Guo Deng

Research output: Contribution to journalArticle

Abstract

Bromodomain PHD finger transcription factor (BPTF), a core subunit of nucleosome-remodeling factor (NURF) complex, plays an important role in chromatin remodeling. However, its precise function and molecular mechanism involved in hepatocellular carcinoma (HCC) growth are still poorly defined. Here, we demonstrated the tumor-promoting role of BPTF in HCC progression. BPTF was highly expressed in HCC cells and tumor tissues of HCC patients compared with normal liver cells and tissues. Knockdown of BPTF inhibited cell proliferation, colony formation and stem cell-like traits in HCC cells. In addition, BPTF knockdown effectively sensitized the anti-tumor effect of chemotherapeutic drugs and induced more apoptosis in HCC cells. Consistently, knockdown of BPTF in a xenograft mouse model also suppressed tumor growth and metastasis accompanied by the suppression of cancer stem cells (CSC)-related protein markers. Moreover, the mechanism study showed that the tumor-promoting role of BPTF in HCC was realized by transcriptionally regulating the expression of human telomerase reverse transcriptase (hTERT). Furthermore, we found that HCC patients with high BPTF expression displayed high hTERT expression, and high BPTF or hTERT expression level was positively correlated with advanced malignancy and poor prognosis in HCC patients. Collectively, our results demonstrate that BPTF promotes HCC growth by targeting hTERT and suggest that the BPTF-hTERT axis maybe a novel and potential therapeutic target in HCC.

LanguageEnglish (US)
Pages427-441
Number of pages15
JournalRedox Biology
Volume20
DOIs
StatePublished - Jan 1 2019

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Neoplastic Stem Cells
Stem cells
Hepatocellular Carcinoma
Growth
Tumors
Neoplasms
human TERT protein
fetal Alzheimer antigen
Tissue
Chromatin Assembly and Disassembly
Nucleosomes
Cell proliferation
Heterografts
Liver
Chromatin
Stem Cells
Cell Proliferation
Apoptosis
Neoplasm Metastasis

Keywords

  • BPTF
  • Cancer stem cell
  • Hepatocellular carcinoma
  • hTERT
  • Stemness

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

Cite this

BPTF promotes hepatocellular carcinoma growth by modulating hTERT signaling and cancer stem cell traits. / Zhao, Xinrui; Zheng, Fufu; Li, Yizhuo; Hao, Jiaojiao; Tang, Zhipeng; Tian, Chunfang; Yang, Qian; Zhu, Tianhua; Diao, Chaoliang; Zhang, Changlin; Chen, Manyu; Hu, Sheng; Guo, Ping; Zhang, Lizhi; Liao, Yina; Yu, Wendan; Chen, Miao; Zou, Lijuan; Guo, Wei; Deng, Wu-Guo.

In: Redox Biology, Vol. 20, 01.01.2019, p. 427-441.

Research output: Contribution to journalArticle

Zhao, X, Zheng, F, Li, Y, Hao, J, Tang, Z, Tian, C, Yang, Q, Zhu, T, Diao, C, Zhang, C, Chen, M, Hu, S, Guo, P, Zhang, L, Liao, Y, Yu, W, Chen, M, Zou, L, Guo, W & Deng, W-G 2019, 'BPTF promotes hepatocellular carcinoma growth by modulating hTERT signaling and cancer stem cell traits' Redox Biology, vol. 20, pp. 427-441. https://doi.org/10.1016/j.redox.2018.10.018
Zhao, Xinrui ; Zheng, Fufu ; Li, Yizhuo ; Hao, Jiaojiao ; Tang, Zhipeng ; Tian, Chunfang ; Yang, Qian ; Zhu, Tianhua ; Diao, Chaoliang ; Zhang, Changlin ; Chen, Manyu ; Hu, Sheng ; Guo, Ping ; Zhang, Lizhi ; Liao, Yina ; Yu, Wendan ; Chen, Miao ; Zou, Lijuan ; Guo, Wei ; Deng, Wu-Guo. / BPTF promotes hepatocellular carcinoma growth by modulating hTERT signaling and cancer stem cell traits. In: Redox Biology. 2019 ; Vol. 20. pp. 427-441.
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abstract = "Bromodomain PHD finger transcription factor (BPTF), a core subunit of nucleosome-remodeling factor (NURF) complex, plays an important role in chromatin remodeling. However, its precise function and molecular mechanism involved in hepatocellular carcinoma (HCC) growth are still poorly defined. Here, we demonstrated the tumor-promoting role of BPTF in HCC progression. BPTF was highly expressed in HCC cells and tumor tissues of HCC patients compared with normal liver cells and tissues. Knockdown of BPTF inhibited cell proliferation, colony formation and stem cell-like traits in HCC cells. In addition, BPTF knockdown effectively sensitized the anti-tumor effect of chemotherapeutic drugs and induced more apoptosis in HCC cells. Consistently, knockdown of BPTF in a xenograft mouse model also suppressed tumor growth and metastasis accompanied by the suppression of cancer stem cells (CSC)-related protein markers. Moreover, the mechanism study showed that the tumor-promoting role of BPTF in HCC was realized by transcriptionally regulating the expression of human telomerase reverse transcriptase (hTERT). Furthermore, we found that HCC patients with high BPTF expression displayed high hTERT expression, and high BPTF or hTERT expression level was positively correlated with advanced malignancy and poor prognosis in HCC patients. Collectively, our results demonstrate that BPTF promotes HCC growth by targeting hTERT and suggest that the BPTF-hTERT axis maybe a novel and potential therapeutic target in HCC.",
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AU - Zhao, Xinrui

AU - Zheng, Fufu

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AU - Hao, Jiaojiao

AU - Tang, Zhipeng

AU - Tian, Chunfang

AU - Yang, Qian

AU - Zhu, Tianhua

AU - Diao, Chaoliang

AU - Zhang, Changlin

AU - Chen, Manyu

AU - Hu, Sheng

AU - Guo, Ping

AU - Zhang, Lizhi

AU - Liao, Yina

AU - Yu, Wendan

AU - Chen, Miao

AU - Zou, Lijuan

AU - Guo, Wei

AU - Deng, Wu-Guo

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AB - Bromodomain PHD finger transcription factor (BPTF), a core subunit of nucleosome-remodeling factor (NURF) complex, plays an important role in chromatin remodeling. However, its precise function and molecular mechanism involved in hepatocellular carcinoma (HCC) growth are still poorly defined. Here, we demonstrated the tumor-promoting role of BPTF in HCC progression. BPTF was highly expressed in HCC cells and tumor tissues of HCC patients compared with normal liver cells and tissues. Knockdown of BPTF inhibited cell proliferation, colony formation and stem cell-like traits in HCC cells. In addition, BPTF knockdown effectively sensitized the anti-tumor effect of chemotherapeutic drugs and induced more apoptosis in HCC cells. Consistently, knockdown of BPTF in a xenograft mouse model also suppressed tumor growth and metastasis accompanied by the suppression of cancer stem cells (CSC)-related protein markers. Moreover, the mechanism study showed that the tumor-promoting role of BPTF in HCC was realized by transcriptionally regulating the expression of human telomerase reverse transcriptase (hTERT). Furthermore, we found that HCC patients with high BPTF expression displayed high hTERT expression, and high BPTF or hTERT expression level was positively correlated with advanced malignancy and poor prognosis in HCC patients. Collectively, our results demonstrate that BPTF promotes HCC growth by targeting hTERT and suggest that the BPTF-hTERT axis maybe a novel and potential therapeutic target in HCC.

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