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Original Research

Open Access

ZNF382 inhibits hepatocellular carcinoma (HCC) cell proliferation and motility and induces apoptosis by up-regulating SOX11

  • Zhi Liu1,2
  • Yang Zhong1,2
  • Jianyu Chen1,2
  • Chuan Lan1,2
  • Jianshui Li1,2
  • Songlin Hou1,2

1Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, 637000 Nanchong City, Sichuan Province, P. R. China

2Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, 637000 Nanchong City, Sichuan Province, P. R. China

DOI: 10.31083/jomh.2021.027 Vol.17,Issue 2,April 2021 pp.77-84

Published: 08 April 2021

*Corresponding Author(s): Zhi Liu E-mail:

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Background and Objective: To detect the mRNA and protein levels of Zinc-finger protein382 (ZNF382) in human hepatocellular carcinoma (HCC) tissues and cell lines and investigate its effects on the cellular processes of HCC cells in vitro.

Methods: Quantitative PCR and Immunoblot assays were respectively conducted to detect the alteration of ZNF382 mRNA and protein levels in HCC human tissues and cell lines. MTT, FCM, wound closure, and transwell assays were performed to detect the effects of ZNF382 on HCC cell proliferation, apoptosis, and motility of HCC cells in vitro. Immunoblot assays were then performed to detect the effects of ZNF382 on the expression of Signal Transducer and Activator of Transcription 3 (STAT3) and SOX11 in HCC cells, and the rescue assays were conducted to confirm the conclusion.

Results: We found ZNF382 was low expression in human HCC tissues and cell lines. ZNF382 suppressed the proliferation and stimulated the apoptosis of HCC cells. Additionally, ZNF382 inhibited the motility of HCC cells in vitro. Mechanically, ZNF382 mediated STAT3/SOX11, and therefore affected the proliferation, apoptosis, and motility of HCC cells.

Conclusion: We showed the abnormal low expression of ZNF382 in human HCC tissues and cell lines, and confirmed the effects of ZNF382 on HCC cellular processes. We thought ZNF382 was a tumor suppressor in HCC.


Zinc-finger protein382 (ZNF382); Hepatocellular carcinoma (HCC); Signal transducer and activator of transcription 3 (STAT3); SOX11; Proliferation; Apoptosis

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Zhi Liu,Yang Zhong,Jianyu Chen,Chuan Lan,Jianshui Li,Songlin Hou. ZNF382 inhibits hepatocellular carcinoma (HCC) cell proliferation and motility and induces apoptosis by up-regulating SOX11. Journal of Men's Health. 2021. 17(2);77-84.


[1] Ludwig DR, Fraum TJ, Cannella R, Ballard DH, Tsai R, Naeem M, et al. Hepatocellular carcinoma (HCC) versus non-HCC: accuracy and reliability of Liver Imaging Reporting and Data System v2018. Abdominal Radiology. 2019; 44: 2116-2132.

[2] Quoc NB, Phuong NDN, Ngan TK, Linh NTM, Cuong PH, Chau NNB. Expression of plasma hsa-miR122 in HBV-related hepatocellular carcinoma (HCC) in Vietnamese patients. MicroRNA. 2018; 7: 92-99.

[3] Ni Q, Chen J, Li X, Xu X, Zhang N, Zhou A, et al. Expression of OTUB1 in hepatocellular carcinoma and its effects on HCC cell migration and invasion. Acta Biochimica et Biophysica Sinica. 2017; 49: 680-688.

[4] Zhang ZM, Tan JX, Wang F, Dao FY, Zhang ZY, Lin H. Early diagnosis of hepatocellular carcinoma using machine learning method. Frontiers in Bioengineering and Biotechnology. 2020; 8: 254.

[5] Wu J, Chai H, Li F, Ren Q, Gu Y. SETD1A augments sorafenib primary resistance via activating YAP in hepatocellular carcinoma. Life Sciences. 2020; 260: 118406.

[6] Zhao B, Hu S, Xiao Q, Fan S, Yu X, Li C, et al. Expression of NOTCH receptors and ligands and prognosis of hepatocellular carcinoma. Biomarkers in Medicine. 2020; 14: 1631-1639.

[7] Schmidt JA, Danielson KG, Duffner ER, Radecki SG, Walker GT, Shelton A, et al. Regulation of the oncogenic phenotype by the nuclear body protein ZC3H8. BMC Cancer. 2018; 18: 759.

[8] Luo K, Yuan W, Zhu C, Li Y, Wang Y, Zeng W, et al. Expression of a novel Krupple-like zinc-finger gene, ZNF382, in human heart. Biochemical and Biophysical Research Communications. 2002; 299: 606-612.

[9] Dang S, Zhou J, Chen Y, Chen P, Ji M, Shi B, et al. Dynamic expression of ZNF382 and its tumor-suppressor role in hepatitis B virus-related hepatocellular carcinogenesis. Oncogene. 2019; 38: 4804-4819.

[10] Ma K, Cao B, Guo M. The detective, prognostic, and predictive value of DNA methylation in human esophageal squamous cell carcinoma. Clinical Epigenetics. 2016; 8: 43.

[11] Liu Z, Zhang J, Gao Y, Pei L, Zhou J, Gu L, et al. Large-scale characterization of DNA methylation changes in human gastric carcinomas with and without metastasis. Clinical Cancer Research. 2014; 20: 4598-4612.

[12] Cheng Y, Geng H, Cheng SH, Liang P, Bai Y, Li J, et al. KRAB zinc finger protein ZNF382 is a proapoptotic tumor suppressor that represses multiple oncogenes and is commonly silenced in multiple carcinomas. Cancer Research. 2010; 70: 6516-6526.

[13] Li L, Li C, Mao H, Du Z, Chan WY, Murray P, et al. Epigenetic inactivation of the CpG demethylase TET1 as a DNA methylation feedback loop in human cancers. Scientific Reports. 2016; 6: 26591.

[14] Chen S, Xiao Z, Zhou J, Yang M, Feng S, Huang Q, et al. ZNF382: a transcription inhibitor down-regulated in multiple tumors due to promoter methylation. Clinica Chimica Acta. 2020; 500: 220-225.

[15] Korkolopoulou P, Levidou G, El-Habr EA, Adamopoulos C, Fragkou P, Boviatsis E, et al. Sox11 expression in astrocytic gliomas: correlation with nestin/c-Met/IDH1-R132H expression phenotypes, p-Stat-3 and survival. British Journal of Cancer. 2013; 108: 2142-2152.

[16] Teng Y, Fan YC, Mu NN, Zhao J, Sun FK, Wang K. Serum SOX11 promoter methylation is a novel biomarker for the diagnosis of Hepatitis B virus-related hepatocellular carcinoma. Neoplasma. 2016; 63: 419-426.

[17] Fei FR, Hu RY, Zhong JM, Gong WW, He QF, Wang H, et al. Morbidity and mortality of malignant tumor in Zhejiang province, 2014. Zhonghua Liu Xing Bing Xue Za Zhi. 2016; 37: 694-698. (In Chinese)

[18] Rezniczek GA, Buggisch J, Sobilo J, Launay A, Lerondel S, Le Pape A, et al. Establishment of a mouse ovarian cancer and peritoneal metastasis model to study intraperitoneal chemotherapy. Cancers. 2020; 12: 3818.

[19] Zhang GQ, Zhong LP, Yang N, Zhao YX. Screening of aptamers and their potential application in targeted diagnosis and therapy of liver cancer. World Journal of Gastroenterology. 2019; 25: 3359-3369.

[20] Cullaro G, Rubin J, Mehta N, Yao F, Verna EC, Lai JC. Sex-based disparities in hepatocellular carcinoma recurrence after liver transplantation. Transplantation. 2020. (in press)

[21] Pei L, He X, Li S, Sun R, Xiang Q, Ren G, et al. KRAB zinc-finger protein 382 regulates epithelial-mesenchymal transition and functions as a tumor suppressor, but is silenced by CpG methylation in gastric cancer. International Journal of Oncology. 2018; 53: 961-972.

[22] Tsang SM, Oliemuller E, Howard BA. Regulatory roles for SOX11 in development, stem cells and cancer. Seminars in Cancer Biology. 2020; 67: 3-11.

[23] Liu Z, Zhong Y, Chen YJ, Chen H. SOX11 regulates apoptosis and cell cycle in hepatocellular carcinoma via Wnt/beta-catenin signaling pathway. Biotechnology and Applied Biochemistry. 2019; 66: 240-246.

[24] Mohanty A, Sandoval N, Phan A, Nguyen TV, Chen RW, Budde E, et al. Regulation of SOX11 expression through CCND1 and STAT3 in mantle cell lymphoma. Blood. 2019; 133: 306-318.

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