NET-1 promotes invasion, adhesion and growth of hepatocellular carcinoma by regulating the expression of BAX, caspase 3, caspase 8 and BCL2

Mingchun Wang; Xiangjun Sun; Yongjun Jiang; Zhen Tan

doi:10.14715/cmb/2018.64.12.8

Issue

Vol. 64 No. 12: Issue 12

Issue Published : October 2, 2018

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NET-1 promotes invasion, adhesion and growth of hepatocellular carcinoma by regulating the expression of BAX, caspase 3, caspase 8 and BCL2

https://doi.org/10.14715/cmb/2018.64.12.8

Mingchun Wang

Department of surgery, Linyi People's Hospital, Linyi, Shandong, China

Xiangjun Sun

Department of hepatobiliary surgery, Linyi People's Hospital, Linyi, Shandong, China

Yongjun Jiang

Department of urology surgery, Linyi Third People's Hospital, Linyi, Shandong, China

Zhen Tan

Department of pathology, Linyi Third People's Hospital, Linyi, Shandong, China

Corresponding Author(s) : Xiangjun Sun

mingchunwang_1@163.com

Cellular and Molecular Biology, Vol. 64 No. 12: Issue 12
Article Published : September 30, 2018

Abstract

Dysregulation of neuroepithelial transforming gene-1 (NET-1) has been shown in hepatocellular carcinoma (HCC) patients. We aimed to evaluate the influence of NET-1 on HCC invasion, adhesion and growth. In vitro cellular functional assays including invasion and adhesion were performed to evaluate the effects of knockdown and overexpression of NET-1. HCC cells were transplanted into nude mice, and tumor growth was assessed. BAX, caspase 3, caspase 8 and BCL2 protein levels were detected by western blot. After transfection with NET-1 siRNA, NET-1 positive ratio in HCC cells significantly decreased. Cell invasion and adhesion assay showed that knockdown of NET-1 reduced the invasion and adhesion ability of HCC cells, whereas overexpression of NET-1 increased the ability. The evaluation of tumor growth revealed that NET-1 knockdown significantly decreased tumor volume and weight, while NET-1 overexpression promoted tumor growth in nude mice. Western blot showed that NET-1 knockdown increased BAX, caspase 3 and caspase 8 expression but decreased BCL2 expression, whereas NET-1 overexpression significantly down-regulated BAX, caspase 3 and caspase 8 expression but increased BCL2 expression. Our data suggest that NET-1 promotes HCC invasion, adhesion and growth by regulating BAX, caspase 3, caspase 8 and BCL2 expression.

Keywords

Growth Hepatocellular carcinoma Invasion NET-1.

Wang, M., Sun, X., Jiang, Y., & Tan, Z. (2018). NET-1 promotes invasion, adhesion and growth of hepatocellular carcinoma by regulating the expression of BAX, caspase 3, caspase 8 and BCL2. Cellular and Molecular Biology, 64(12), 37–41. https://doi.org/10.14715/cmb/2018.64.12.8

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References

Hartke J, Johnson M, Ghabril M. The diagnosis and treatment of hepatocellular carcinoma. Semin Diagn Pathol. 2017;34(2):153-159.
Desai JR, Ochoa S, Prins PA, He AR. Systemic therapy for advanced hepatocellular carcinoma: an update. J Gastrointest Oncol. 2017;8(2):243-255.
Bupathi M, Kaseb A, Janku F. Angiopoietin 2 as a therapeutic target in hepatocellular carcinoma treatment: current perspectives. Onco Targets Ther. 2014;7:1927-32.
Wang PL, Liu B, Xia Y, Pan CF, Ma T, Chen YJ. Long non-coding RNA-Low Expression in Tumor inhibits the invasion and metastasis of esophageal squamous cell carcinoma by regulating p53 expression. Mol Med Rep. 2016;13(4):3074-82.
Li JP, Liu Y, Yin YH. ARHGAP1 overexpression inhibits proliferation, migration and invasion of C-33A and SiHa cell lines. Onco Targets Ther. 2017;10:691-701.
Murray D, Horgan G, Macmathuna P, Doran P. NET1-mediated RhoA activation facilitates lysophosphatidic acid-induced cell migration and invasion in gastric cancer. Br J Cancer. 2008;99(8):1322-9.
Ye K, Wang Z, Zhang G, Liang S. Prognostic significance of neuroepithelial transforming protein 1 in hepatocellular carcinoma. J Invest Surg. 2010;23(3):163-9.
Fang L, Zhu J, Ma Y, Hong C, Xiao S, Jin L. Neuroepithelial transforming gene 1 functions as a potential prognostic marker for patients with non-small cell lung cancer. Mol Med Rep. 2015;12(5):7439-46.
Shen SQ, Li K, Zhu N, Nakao A. Expression and clinical significance of NET-1
and PCNA in hepatocellular carcinoma. Med Oncol. 2008;25(3):341-5.
Wang GL, Chen L, Wei YZ, et al. The effect of NET-1 on the proliferation, migration and endocytosis of the SMMC-7721 HCC cell line. Oncol Rep. 2012;27(6):1944-52.
Han X, Cheng W, Jing H, Zhang JW, Tang LL. Neuroepithelial transforming protein 1 short interfering RNA-mediated gene silencing with microbubble and ultrasound exposure inhibits the proliferation of hepatic carcinoma cells in vitro. J Ultrasound Med. 2012;31(6):853-61.
Llovet JM, Zucman-Rossi J, Pikarsky E, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016;2:16018.
Boyle DA. Hepatocellular Carcinoma: Implications for Asian-Pacific Oncology Nurses. Asia Pac J Oncol Nurs. 2017;4(2):98-103.
Xu J, Stolk JA, Zhang X, et al. Identification of differentially expressed genes in human prostate cancer using subtraction and microarray. Cancer
Res. 2000;60(6):1677-82.
He S, Wei YZ, Wang GL, et al. Study of RNA Interference Targeting NET-1 Combination with Sorafenib for Hepatocellular Carcinoma Therapy In Vitro and In Vivo. Gastroenterol Res Pract. 2013;2013:685150.
Pirocanac EC, Nassirpour R, Yang M, et al.Bax-induction gene therapy of pancreatic cancer. J Surg Res. 2002;106(2):346-51.
Guo XZ, Shao XD, Liu MP, et al. Effect of bax, bcl-2 and bcl-xL on regulating apoptosis in tissues of normal liver and hepatocellular carcinoma. World J
Gastroenterol. 2002;8(6):1059-62.
Liu YK, Chen KH, Leu YL, et al. Ethanol extracts of Cinnamomum kanehirai Hayata leaves induce apoptosis in human hepatoma cell through caspase-3 cascade. Onco Targets Ther. 2014;8:99-109.
Sun BH, Zhang J, Wang BJ, et al. Analysis of in vivo patterns of caspase 3 gene expression in primary hepatocellular carcinoma and its relationship to p21(WAF1) expression and hepatic apoptosis. World J Gastroenterol. 2000;6(3):356-360.
Tummers B, Green DR. Caspase-8: regulating life and death. Immunol Rev.
;277(1):76-89.
Soung YH, Lee JW, Kim SY, et al. Caspase-8 gene is frequently inactivated by the frameshift somatic mutation 1225_1226delTG in hepatocellular carcinomas. Oncogene. 2005;24(1):141-7.
Youle RJ, Strasser A. The BCL-2 protein family:opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2008;9(1):47-59.
Chun E, Lee KY. Bcl-2 and Bcl-xL are important for the induction of paclitaxel resistance in human hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2004;315(3):771-9.

References

Hartke J, Johnson M, Ghabril M. The diagnosis and treatment of hepatocellular carcinoma. Semin Diagn Pathol. 2017;34(2):153-159.

Desai JR, Ochoa S, Prins PA, He AR. Systemic therapy for advanced hepatocellular carcinoma: an update. J Gastrointest Oncol. 2017;8(2):243-255.

Bupathi M, Kaseb A, Janku F. Angiopoietin 2 as a therapeutic target in hepatocellular carcinoma treatment: current perspectives. Onco Targets Ther. 2014;7:1927-32.

Wang PL, Liu B, Xia Y, Pan CF, Ma T, Chen YJ. Long non-coding RNA-Low Expression in Tumor inhibits the invasion and metastasis of esophageal squamous cell carcinoma by regulating p53 expression. Mol Med Rep. 2016;13(4):3074-82.

Li JP, Liu Y, Yin YH. ARHGAP1 overexpression inhibits proliferation, migration and invasion of C-33A and SiHa cell lines. Onco Targets Ther. 2017;10:691-701.

Murray D, Horgan G, Macmathuna P, Doran P. NET1-mediated RhoA activation facilitates lysophosphatidic acid-induced cell migration and invasion in gastric cancer. Br J Cancer. 2008;99(8):1322-9.

Ye K, Wang Z, Zhang G, Liang S. Prognostic significance of neuroepithelial transforming protein 1 in hepatocellular carcinoma. J Invest Surg. 2010;23(3):163-9.

Fang L, Zhu J, Ma Y, Hong C, Xiao S, Jin L. Neuroepithelial transforming gene 1 functions as a potential prognostic marker for patients with non-small cell lung cancer. Mol Med Rep. 2015;12(5):7439-46.

Shen SQ, Li K, Zhu N, Nakao A. Expression and clinical significance of NET-1

and PCNA in hepatocellular carcinoma. Med Oncol. 2008;25(3):341-5.

Wang GL, Chen L, Wei YZ, et al. The effect of NET-1 on the proliferation, migration and endocytosis of the SMMC-7721 HCC cell line. Oncol Rep. 2012;27(6):1944-52.

Han X, Cheng W, Jing H, Zhang JW, Tang LL. Neuroepithelial transforming protein 1 short interfering RNA-mediated gene silencing with microbubble and ultrasound exposure inhibits the proliferation of hepatic carcinoma cells in vitro. J Ultrasound Med. 2012;31(6):853-61.

Llovet JM, Zucman-Rossi J, Pikarsky E, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016;2:16018.

Boyle DA. Hepatocellular Carcinoma: Implications for Asian-Pacific Oncology Nurses. Asia Pac J Oncol Nurs. 2017;4(2):98-103.

Xu J, Stolk JA, Zhang X, et al. Identification of differentially expressed genes in human prostate cancer using subtraction and microarray. Cancer

Res. 2000;60(6):1677-82.

He S, Wei YZ, Wang GL, et al. Study of RNA Interference Targeting NET-1 Combination with Sorafenib for Hepatocellular Carcinoma Therapy In Vitro and In Vivo. Gastroenterol Res Pract. 2013;2013:685150.

Pirocanac EC, Nassirpour R, Yang M, et al.Bax-induction gene therapy of pancreatic cancer. J Surg Res. 2002;106(2):346-51.

Guo XZ, Shao XD, Liu MP, et al. Effect of bax, bcl-2 and bcl-xL on regulating apoptosis in tissues of normal liver and hepatocellular carcinoma. World J

Gastroenterol. 2002;8(6):1059-62.

Liu YK, Chen KH, Leu YL, et al. Ethanol extracts of Cinnamomum kanehirai Hayata leaves induce apoptosis in human hepatoma cell through caspase-3 cascade. Onco Targets Ther. 2014;8:99-109.

Sun BH, Zhang J, Wang BJ, et al. Analysis of in vivo patterns of caspase 3 gene expression in primary hepatocellular carcinoma and its relationship to p21(WAF1) expression and hepatic apoptosis. World J Gastroenterol. 2000;6(3):356-360.

Tummers B, Green DR. Caspase-8: regulating life and death. Immunol Rev.

;277(1):76-89.

Soung YH, Lee JW, Kim SY, et al. Caspase-8 gene is frequently inactivated by the frameshift somatic mutation 1225_1226delTG in hepatocellular carcinomas. Oncogene. 2005;24(1):141-7.

Youle RJ, Strasser A. The BCL-2 protein family:opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2008;9(1):47-59.

Chun E, Lee KY. Bcl-2 and Bcl-xL are important for the induction of paclitaxel resistance in human hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2004;315(3):771-9.

Author biographies is not available.