ANKHD1 is required for SMYD3 to promote tumor metastasis in hepatocellular carcinoma

Zhenyu Zhou, Hai Jiang, Kangsheng Tu, Wei Yu, Jianlong Zhang, Zhigang Hu, Heyun Zhang, Dake Hao, Pinbo Huang, Jie Wang, Aijun Wang, Zhiyu Xiao, Chuanchao He

Research output: Contribution to journalArticle

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Abstract

Absract: Background: Tumor metastasis is the major reason for poor prognosis of hepatocellular carcinoma (HCC) patients after hepatic resection. SMYD3 has been demonstrated to promote liver tumor metastasis in mice. However, the detailed molecular mechanism is still largely unknown. Methods: The effect of SMYD3 on invasiveness and metastasis of HCC was analyzed by immunohistochemistry, migration assay, invasion assay, wound healing assay and in vivo lung metastasis assay. Mass spectrometry analysis was conducted using proteins pulled down by H3K4me3 antibody in SMYD3-overexpressing cells. Luciferase reporter, chromatin immunoprecipitation, Electrophoretic mobility shift assay were used to measure the regulation of SLUG transcription by SMYD3-ANKHD1. In addition, the role of SMYD3-ANKHD1 in determining clinical outcomes for HCC patients was investigated by immunohistochemistry in 243 HCC tissues. Results: SMYD3 was an independent prognostic factor of HCC and promoted migration and invasion of human HCC cells. ANKHD1 was identified by mass spectrometry as a co-regulator with SMYD3. ANKHD1 interacted with H3K4me3 when cells were overexpressing SMYD3. The pro-migratory and pro-invasive effects of SMYD3 were attenuated when ANKHD1 was knocked down by siRNA. Furthermore, we found that SMYD3 bound and activated the SLUG gene promoter in a manner associated with elevating H3K4me3, H3K9Ac and H3K14Ac. Knockdown of ANKHD1 could attenuate the SMYD3-dependent activation of Slug expression. We further detected the expression of SMYD3 and ANKHD1 in 243 HCC patients and found that patients with positive coexpression of SMYD3 and ANKHD1 (SMYD3+ANKHD1+) had the shortest overall and recurrence-free survival. Conclusion: Our findings provide a novel molecular mechanism for the SMYD3-regulated HCC migration and metastasis, and indicates that SMYD3-ANKHD1 may be a potential target for treating HCC.

Original languageEnglish (US)
Article number18
JournalJournal of Experimental and Clinical Cancer Research
Volume38
Issue number1
DOIs
StatePublished - Jan 15 2019

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Hepatocellular Carcinoma
Neoplasm Metastasis
Neoplasms
Mass Spectrometry
Immunohistochemistry
Gastropoda
Chromatin Immunoprecipitation
Liver
Electrophoretic Mobility Shift Assay
Luciferases
Wound Healing
Small Interfering RNA
Recurrence
Lung
Survival
Antibodies
Genes
Proteins

Keywords

  • ANKHD1
  • Hepatocellular carcinoma
  • Metastasis
  • Slug
  • SMYD3

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

ANKHD1 is required for SMYD3 to promote tumor metastasis in hepatocellular carcinoma. / Zhou, Zhenyu; Jiang, Hai; Tu, Kangsheng; Yu, Wei; Zhang, Jianlong; Hu, Zhigang; Zhang, Heyun; Hao, Dake; Huang, Pinbo; Wang, Jie; Wang, Aijun; Xiao, Zhiyu; He, Chuanchao.

In: Journal of Experimental and Clinical Cancer Research, Vol. 38, No. 1, 18, 15.01.2019.

Research output: Contribution to journalArticle

Zhou, Z, Jiang, H, Tu, K, Yu, W, Zhang, J, Hu, Z, Zhang, H, Hao, D, Huang, P, Wang, J, Wang, A, Xiao, Z & He, C 2019, 'ANKHD1 is required for SMYD3 to promote tumor metastasis in hepatocellular carcinoma' Journal of Experimental and Clinical Cancer Research, vol. 38, no. 1, 18. https://doi.org/10.1186/s13046-018-1011-0
Zhou, Zhenyu ; Jiang, Hai ; Tu, Kangsheng ; Yu, Wei ; Zhang, Jianlong ; Hu, Zhigang ; Zhang, Heyun ; Hao, Dake ; Huang, Pinbo ; Wang, Jie ; Wang, Aijun ; Xiao, Zhiyu ; He, Chuanchao. / ANKHD1 is required for SMYD3 to promote tumor metastasis in hepatocellular carcinoma. In: Journal of Experimental and Clinical Cancer Research. 2019 ; Vol. 38, No. 1.
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abstract = "Absract: Background: Tumor metastasis is the major reason for poor prognosis of hepatocellular carcinoma (HCC) patients after hepatic resection. SMYD3 has been demonstrated to promote liver tumor metastasis in mice. However, the detailed molecular mechanism is still largely unknown. Methods: The effect of SMYD3 on invasiveness and metastasis of HCC was analyzed by immunohistochemistry, migration assay, invasion assay, wound healing assay and in vivo lung metastasis assay. Mass spectrometry analysis was conducted using proteins pulled down by H3K4me3 antibody in SMYD3-overexpressing cells. Luciferase reporter, chromatin immunoprecipitation, Electrophoretic mobility shift assay were used to measure the regulation of SLUG transcription by SMYD3-ANKHD1. In addition, the role of SMYD3-ANKHD1 in determining clinical outcomes for HCC patients was investigated by immunohistochemistry in 243 HCC tissues. Results: SMYD3 was an independent prognostic factor of HCC and promoted migration and invasion of human HCC cells. ANKHD1 was identified by mass spectrometry as a co-regulator with SMYD3. ANKHD1 interacted with H3K4me3 when cells were overexpressing SMYD3. The pro-migratory and pro-invasive effects of SMYD3 were attenuated when ANKHD1 was knocked down by siRNA. Furthermore, we found that SMYD3 bound and activated the SLUG gene promoter in a manner associated with elevating H3K4me3, H3K9Ac and H3K14Ac. Knockdown of ANKHD1 could attenuate the SMYD3-dependent activation of Slug expression. We further detected the expression of SMYD3 and ANKHD1 in 243 HCC patients and found that patients with positive coexpression of SMYD3 and ANKHD1 (SMYD3+ANKHD1+) had the shortest overall and recurrence-free survival. Conclusion: Our findings provide a novel molecular mechanism for the SMYD3-regulated HCC migration and metastasis, and indicates that SMYD3-ANKHD1 may be a potential target for treating HCC.",
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AU - Zhou, Zhenyu

AU - Jiang, Hai

AU - Tu, Kangsheng

AU - Yu, Wei

AU - Zhang, Jianlong

AU - Hu, Zhigang

AU - Zhang, Heyun

AU - Hao, Dake

AU - Huang, Pinbo

AU - Wang, Jie

AU - Wang, Aijun

AU - Xiao, Zhiyu

AU - He, Chuanchao

PY - 2019/1/15

Y1 - 2019/1/15

N2 - Absract: Background: Tumor metastasis is the major reason for poor prognosis of hepatocellular carcinoma (HCC) patients after hepatic resection. SMYD3 has been demonstrated to promote liver tumor metastasis in mice. However, the detailed molecular mechanism is still largely unknown. Methods: The effect of SMYD3 on invasiveness and metastasis of HCC was analyzed by immunohistochemistry, migration assay, invasion assay, wound healing assay and in vivo lung metastasis assay. Mass spectrometry analysis was conducted using proteins pulled down by H3K4me3 antibody in SMYD3-overexpressing cells. Luciferase reporter, chromatin immunoprecipitation, Electrophoretic mobility shift assay were used to measure the regulation of SLUG transcription by SMYD3-ANKHD1. In addition, the role of SMYD3-ANKHD1 in determining clinical outcomes for HCC patients was investigated by immunohistochemistry in 243 HCC tissues. Results: SMYD3 was an independent prognostic factor of HCC and promoted migration and invasion of human HCC cells. ANKHD1 was identified by mass spectrometry as a co-regulator with SMYD3. ANKHD1 interacted with H3K4me3 when cells were overexpressing SMYD3. The pro-migratory and pro-invasive effects of SMYD3 were attenuated when ANKHD1 was knocked down by siRNA. Furthermore, we found that SMYD3 bound and activated the SLUG gene promoter in a manner associated with elevating H3K4me3, H3K9Ac and H3K14Ac. Knockdown of ANKHD1 could attenuate the SMYD3-dependent activation of Slug expression. We further detected the expression of SMYD3 and ANKHD1 in 243 HCC patients and found that patients with positive coexpression of SMYD3 and ANKHD1 (SMYD3+ANKHD1+) had the shortest overall and recurrence-free survival. Conclusion: Our findings provide a novel molecular mechanism for the SMYD3-regulated HCC migration and metastasis, and indicates that SMYD3-ANKHD1 may be a potential target for treating HCC.

AB - Absract: Background: Tumor metastasis is the major reason for poor prognosis of hepatocellular carcinoma (HCC) patients after hepatic resection. SMYD3 has been demonstrated to promote liver tumor metastasis in mice. However, the detailed molecular mechanism is still largely unknown. Methods: The effect of SMYD3 on invasiveness and metastasis of HCC was analyzed by immunohistochemistry, migration assay, invasion assay, wound healing assay and in vivo lung metastasis assay. Mass spectrometry analysis was conducted using proteins pulled down by H3K4me3 antibody in SMYD3-overexpressing cells. Luciferase reporter, chromatin immunoprecipitation, Electrophoretic mobility shift assay were used to measure the regulation of SLUG transcription by SMYD3-ANKHD1. In addition, the role of SMYD3-ANKHD1 in determining clinical outcomes for HCC patients was investigated by immunohistochemistry in 243 HCC tissues. Results: SMYD3 was an independent prognostic factor of HCC and promoted migration and invasion of human HCC cells. ANKHD1 was identified by mass spectrometry as a co-regulator with SMYD3. ANKHD1 interacted with H3K4me3 when cells were overexpressing SMYD3. The pro-migratory and pro-invasive effects of SMYD3 were attenuated when ANKHD1 was knocked down by siRNA. Furthermore, we found that SMYD3 bound and activated the SLUG gene promoter in a manner associated with elevating H3K4me3, H3K9Ac and H3K14Ac. Knockdown of ANKHD1 could attenuate the SMYD3-dependent activation of Slug expression. We further detected the expression of SMYD3 and ANKHD1 in 243 HCC patients and found that patients with positive coexpression of SMYD3 and ANKHD1 (SMYD3+ANKHD1+) had the shortest overall and recurrence-free survival. Conclusion: Our findings provide a novel molecular mechanism for the SMYD3-regulated HCC migration and metastasis, and indicates that SMYD3-ANKHD1 may be a potential target for treating HCC.

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KW - Hepatocellular carcinoma

KW - Metastasis

KW - Slug

KW - SMYD3

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