Clinical significance of HDAC9 in hepatocellular carcinoma

Yuzhi Hu; Lei Sun; Shaofu Tao; Min Dai; Yandong Wang; Yong Li; Jiebin Wu

doi:10.14715/10.14715/cmb/2019.65.4.4

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Vol. 65 No. 4: Issue 4

Issue Published : May 12, 2019

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Clinical significance of HDAC9 in hepatocellular carcinoma

https://doi.org/10.14715/10.14715/cmb/2019.65.4.4

Yuzhi Hu

Department of Hepatobiliary Surgery, the Second People's Hospital of Wuhu. No. 259, Jiuhua Middle Road, 241001 Wuhu City, Anhui Province, China

Lei Sun

Department of Hepatobiliary Surgery, the Second People's Hospital of Wuhu. No. 259, Jiuhua Middle Road, 241001 Wuhu City, Anhui Province, China

Shaofu Tao

Department of Hepatobiliary Surgery, the Second People's Hospital of Wuhu. No. 259, Jiuhua Middle Road, 241001 Wuhu City, Anhui Province, China

Min Dai

Department of Pathology, the Second People's Hospital of Wuhu. No. 259, Jiuhua Middle Road, 241001 Wuhu City, Anhui Province, China

Yandong Wang

Department of Gastrointestinal Surgery, the Second People's Hospital of Wuhu. No. 259, Jiuhua Middle Road, 241001 Wuhu City, Anhui Province, China

Yong Li

Department of Pathology, the Second People's Hospital of Wuhu. No. 259, Jiuhua Middle Road, 241001 Wuhu City, Anhui Province, China

Jiebin Wu

Department of Hepatobiliary Surgery, the Second People's Hospital of Wuhu. No. 259, Jiuhua Middle Road, 241001 Wuhu City, Anhui Province, China

Corresponding Author(s) : Jiebin Wu

rfksp0@163.com

Cellular and Molecular Biology, Vol. 65 No. 4: Issue 4
Article Published : April 30, 2019

Abstract

In recent years, most related studies have found that chronic hepatitis B virus infection is the main cause of hepatocellular carcinoma (HCC), but the specific pathogenesis is still unclear. To investigate the function of HDAC in hepatocellular carcinoma (HCC), this study used qRT-PCR to determine the expression levels of miR-376a and HDAC9 mNRA in HCC and para-cancerous tissues. The clinical significance of HDAC9 in HCC was assessed in a study cohort containing 37 patients with HCC using immunohistochemistry. The expression level of miR-376a in liver cancer tissues was significantly lower than that in para-cancerous tissues, while the expression level of HDAC9 mRNA in liver cancer tissue was significantly higher than that in para-cancerous tissues. The expression of HDAC9 occurred mainly in the nucleus. There was a significant correlation between tumor differentiation and HDAC9. Survival analysis showed that HCC patients with higher HDAC9 expression had poorer prognosis, and subsequent multivariate analysis showed that HDAC9 expression level was an independent predictor. There was a definite correlation between HDAC9 and the expressions of AFP and Ki67. These results suggest that the expression level of HDAC9 in HCC is abnormally high while the expression level of miR-376a is significantly decreased, indicating that HDAC9 may be a potential prognostic indicator of HCC.

Keywords

Biological tissue microarray Prognosis Immunohistochemistry Hepatocellular carcinoma HDAC9 Ki67 AFP.

Hu, Y., Sun, L., Tao, S., Dai, M., Wang, Y., Li, Y., & Wu, J. (2019). Clinical significance of HDAC9 in hepatocellular carcinoma. Cellular and Molecular Biology, 65(4), 23–28. https://doi.org/10.14715/10.14715/cmb/2019.65.4.4

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References

Zhu ZX, Huang JW, Liao MH, Zeng Y. Treatment strategy for hepatocellular carcinoma in China: radiofrequency ablation versus liver resection. Jpn J Clin Oncol 2016; 46: 1075-1080
Levrero M, Zucman-Rossi J. Mechanisms of HBV-induced hepatocellular carcinoma. J Hepatol 2016; 64: 84-101.
Abdeahad H, Avan A, Pashirzad M, Khazaei M, Soleimanpour S, Ferns GA, et al. The prognostic potential of long noncoding RNA HOTAIR expression in human digestive system carcinomas: A meta-analysis. J Cell Physiol 2018.
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Buurman R, Sandbothe M, Schlegelberger B, Skawran B. HDAC inhibition activates the apoptosome via Apaf1 upregulation in hepatocellular carcinoma. Eur J Med Res 2016; 21: 26.
Jamiruddin MR, Kaitsuka T, Hakim F, Fujimura A, Wei FY, Saitoh H, et al. HDAC9 regulates the alternative lengthening of telomere (ALT) pathway via the formation of ALT-associated PML bodies. Biochem Biophys Res Commun 2016; 481: 25-30.
Lapierre M, Linares A, Dalvai M, Duraffourd C, Bonnet S, Boulahtouf A, et al. Histone deacetylase 9 regulates breast cancer cell proliferation and the response to histone deacetylase inhibitors. Oncotarget 2016; 7: 19693-19708.
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Salgado E, Bian X, Feng A, Shim H, Liang Z. HDAC9 overexpression confers invasive and angiogenic potential to triple negative breast cancer cells via modulating microRNA-206. Biochem Biophys Res Commun 2018; 503: 1087-1091.
Huang Y, Jian W, Zhao J, Wang G. Overexpression of HDAC9 is associated with poor prognosis and tumor progression of breast cancer in Chinese females. Onco Targets Ther 2018; 11: 2177-2184.
Rastogi B, Kumar A, Raut SK, Panda NK, Rattan V, Joshi N, et al. Downregulation of miR-377 Promotes Oral Squamous Cell Carcinoma Growth and Migration by Targeting HDAC9. Cancer Invest 2017; 35: 152-162.
Rastogi B, Raut SK, Panda NK, Rattan V, Radotra BD, Khullar M. Overexpression of HDAC9 promotes oral squamous cell carcinoma growth, regulates cell cycle progression, and inhibits apoptosis. Mol Cell Biochem 2016; 415: 183-196.
Zhang Y, Wu D, Xia F, Xian H, Zhu X, Cui H, et al. Downregulation of HDAC9 inhibits cell proliferation and tumor formation by inducing cell cycle arrest in retinoblastoma. Biochem Biophys Res Commun 2016; 473: 600-606.
Gil VS, Bhagat G, Howell L, Zhang J, Kim CH, Stengel S, et al. Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice. Dis Model Mech 2016; 9: 1483-1495.
Mehta N, Dodge JL, Roberts JP, Hirose R, Yao FY. Alpha-fetoprotein Decrease from >1000 to <500 ng/ml in Patients with Hepatocellular Carcinoma Leads to Improved Post-Transplant Outcomes. Hepatology 2018.
Zheng Y, Chen H, Yin M, Ye X, Chen G, Zhou X, et al. MiR-376a and histone deacetylation 9 form a regulatory circuitry in hepatocellular carcinoma. Cell Physiol Biochem 2015; 35: 729-739.
Zheng Y, Yin L, Chen H, Yang S, Pan C, Lu S, et al. miR-376a suppresses proliferation and induces apoptosis in hepatocellular carcinoma. FEBS letters 2012; 586: 2396-2403.
Jin J, Zhang XY, Shi JL, Xue XF, Lu LL, Lu JH, et al. Application of AFP whole blood one-step rapid detection kit in screening for HCC in Qidong. Am J Cancer Res 2017; 7: 1384-1388.
Notarpaolo A, Layese R, Magistri P, Gambato M, Colledan M, Magini G, et al. Validation of the AFP model as a predictor of HCC recurrence in patients with viral hepatitis-related cirrhosis who had received a liver transplant for HCC. J Hepatol 2017; 66: 552-559.
Wang T, Zhang KH, Hu PP, Wan QS, Han FL, Zhou JM, et al. Combination of dual serum fluorescence, AFP and hepatic function tests is valuable to identify HCC in AFP-elevated liver diseases. Oncotarget 2017; 8: 97758-97768.

References

Zhu ZX, Huang JW, Liao MH, Zeng Y. Treatment strategy for hepatocellular carcinoma in China: radiofrequency ablation versus liver resection. Jpn J Clin Oncol 2016; 46: 1075-1080

Levrero M, Zucman-Rossi J. Mechanisms of HBV-induced hepatocellular carcinoma. J Hepatol 2016; 64: 84-101.

Abdeahad H, Avan A, Pashirzad M, Khazaei M, Soleimanpour S, Ferns GA, et al. The prognostic potential of long noncoding RNA HOTAIR expression in human digestive system carcinomas: A meta-analysis. J Cell Physiol 2018.

Vilchez V, Turcios L, Marti F, Gedaly R. Targeting Wnt/beta-catenin pathway in hepatocellular carcinoma treatment. World J Gastroenterol 2016; 22: 823-832.

Buurman R, Sandbothe M, Schlegelberger B, Skawran B. HDAC inhibition activates the apoptosome via Apaf1 upregulation in hepatocellular carcinoma. Eur J Med Res 2016; 21: 26.

Jamiruddin MR, Kaitsuka T, Hakim F, Fujimura A, Wei FY, Saitoh H, et al. HDAC9 regulates the alternative lengthening of telomere (ALT) pathway via the formation of ALT-associated PML bodies. Biochem Biophys Res Commun 2016; 481: 25-30.

Lapierre M, Linares A, Dalvai M, Duraffourd C, Bonnet S, Boulahtouf A, et al. Histone deacetylase 9 regulates breast cancer cell proliferation and the response to histone deacetylase inhibitors. Oncotarget 2016; 7: 19693-19708.

Lakshmaiah KC, Jacob LA, Aparna S, Lokanatha D, Saldanha SC. Epigenetic therapy of cancer with histone deacetylase inhibitors. J Cancer Res Ther 2014; 10: 469-478.

Salgado E, Bian X, Feng A, Shim H, Liang Z. HDAC9 overexpression confers invasive and angiogenic potential to triple negative breast cancer cells via modulating microRNA-206. Biochem Biophys Res Commun 2018; 503: 1087-1091.

Huang Y, Jian W, Zhao J, Wang G. Overexpression of HDAC9 is associated with poor prognosis and tumor progression of breast cancer in Chinese females. Onco Targets Ther 2018; 11: 2177-2184.

Rastogi B, Kumar A, Raut SK, Panda NK, Rattan V, Joshi N, et al. Downregulation of miR-377 Promotes Oral Squamous Cell Carcinoma Growth and Migration by Targeting HDAC9. Cancer Invest 2017; 35: 152-162.

Rastogi B, Raut SK, Panda NK, Rattan V, Radotra BD, Khullar M. Overexpression of HDAC9 promotes oral squamous cell carcinoma growth, regulates cell cycle progression, and inhibits apoptosis. Mol Cell Biochem 2016; 415: 183-196.

Zhang Y, Wu D, Xia F, Xian H, Zhu X, Cui H, et al. Downregulation of HDAC9 inhibits cell proliferation and tumor formation by inducing cell cycle arrest in retinoblastoma. Biochem Biophys Res Commun 2016; 473: 600-606.

Gil VS, Bhagat G, Howell L, Zhang J, Kim CH, Stengel S, et al. Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice. Dis Model Mech 2016; 9: 1483-1495.

Mehta N, Dodge JL, Roberts JP, Hirose R, Yao FY. Alpha-fetoprotein Decrease from >1000 to <500 ng/ml in Patients with Hepatocellular Carcinoma Leads to Improved Post-Transplant Outcomes. Hepatology 2018.

Zheng Y, Chen H, Yin M, Ye X, Chen G, Zhou X, et al. MiR-376a and histone deacetylation 9 form a regulatory circuitry in hepatocellular carcinoma. Cell Physiol Biochem 2015; 35: 729-739.

Zheng Y, Yin L, Chen H, Yang S, Pan C, Lu S, et al. miR-376a suppresses proliferation and induces apoptosis in hepatocellular carcinoma. FEBS letters 2012; 586: 2396-2403.

Jin J, Zhang XY, Shi JL, Xue XF, Lu LL, Lu JH, et al. Application of AFP whole blood one-step rapid detection kit in screening for HCC in Qidong. Am J Cancer Res 2017; 7: 1384-1388.

Notarpaolo A, Layese R, Magistri P, Gambato M, Colledan M, Magini G, et al. Validation of the AFP model as a predictor of HCC recurrence in patients with viral hepatitis-related cirrhosis who had received a liver transplant for HCC. J Hepatol 2017; 66: 552-559.

Wang T, Zhang KH, Hu PP, Wan QS, Han FL, Zhou JM, et al. Combination of dual serum fluorescence, AFP and hepatic function tests is valuable to identify HCC in AFP-elevated liver diseases. Oncotarget 2017; 8: 97758-97768.

Author biographies is not available.