HepG2和HepG2.2.15细胞ENPP2/EZH2表达变化及其对细胞增殖和侵袭力的影响*

doi:10.3969/j.issn.1672-5069.2025.04.005

实用肝脏病杂志 ›› 2025, Vol. 28 ›› Issue (4): 497-500.doi: 10.3969/j.issn.1672-5069.2025.04.005

HepG2和HepG2.2.15细胞ENPP2/EZH2表达变化及其对细胞增殖和侵袭力的影响^*

邓万玉, 黄子乐, 刘泽妍, 秦培毓, 刘娜

334001 江西省上饶市上饶师范学院生命科学学院(邓万玉,黄子乐,刘泽妍,秦培毓);上饶市人民医院病理科(刘娜)

收稿日期:2024-11-17 出版日期:2025-07-10 发布日期:2025-07-14
通讯作者: 刘娜,E-mail:liuna_1008@163.com
作者简介:邓万玉,女,37岁,医学博士,副教授。主要从事病毒性肝脏疾病致病机理研究。E-mail: wanyu0330@126.com
基金资助:
^*国家自然科学基金资助项目(编号:82260603);江西省自然科学基金资助项目(编号:20224BAB206005)

Ectonucleotide pyrophosphatase/phosphodiesterase 2 and enhancer of Zeste homolog 2 in HepG2 and HepG2.2.15 cells and their impact on cell proliferation and invasiveness

Deng Wanyu, Huang Zile, Liu Zeyan, et al

College of Life Science, Shangrao Normal University, Shangrao 334001, Jiangxi Province, China

Received:2024-11-17 Online:2025-07-10 Published:2025-07-14

摘要/Abstract

摘要： 目的探究外核苷酸焦磷酸酶/磷酸二酯酶(ENPP2)和Zeste增强子同源物2(EZH2)在乙型肝炎病毒(HBV)阳性肝癌细胞的促肿瘤作用。方法合成针对ENPP2和EZH2的siRNA,以敲除HepG2细胞和稳定转染HBV基因组的HepG2.2.15细胞两种蛋白表达。分别取HepG2、HepG2.2.15、转染pSM2质粒的HepG2细胞(HepG2/pSM2)、转染siENPP2或siEZH2的HepG2.2.15细胞,采用RT-PCR和Western blot法检测细胞ENPP2和EZH2 mRNA水平及其蛋白表达,采用CCK-8法检测细胞增殖,采用Trans-well试验检测肝癌细胞侵袭能力。结果与HepG2细胞比,瞬时转染HBV表达质粒的HepG2和稳定转染HBV基因组的HepG2.2.15细胞ENPP2和EZH2 mRNA水平都显著升高(P<0.001),转染HBV的肝癌细胞ENPP2和EZH2蛋白表达也明显上调(P<0.001);HepG2.2.15细胞增殖和侵袭能力显著强于HepG2细胞(P<0.01),而抑制ENPP2或EZH2表达的HepG2.2.15细胞增殖和侵袭能力也明显减弱(P<0.01)。结论 HBV阳性肝癌细胞促肿瘤因子ENPP2和EZH2表达增强,细胞的增殖和侵袭力也增强,可能与肝癌发生有关。

关键词: HepG2细胞, HepG2.2.15细胞, 外核苷酸焦磷酸酶/磷酸二酯酶, Zeste增强子同源物2, 细胞增殖, 细胞侵袭, 体外

Abstract: Objective The aim of this experiment was to investigate tumor-promoting elements, e.g., ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) and enhancer of Zeste homolog 2 (EZH2) in HepG2 and HepG2.2.15 cells and their impact on cell proliferation and invasiveness. Methods For inhibition of ENPP2 and EZH2 expression, siRNAs were synthesized, and HepG2, HepG2.2.15, pSM2 plasmid-transfected HepG2(HepG2/pSM2) and siENPP2 or siEZH2-transfected HepG2.2.15 cells were harvested. ENPP2 and EZH2 mRNAs were detected by real-time PCR and their expression was detected by Western blot. Proliferation and invasion of cells were detected by CCK-8 and Trans-well movement. Results ENPP2 and EZH2 mRNA loads in transient HBV-plasmid transfected HepG2 cells or HepG2.2.15 cells with stable HBV infection increased greatly, compared to those in HepG2 cells (P<0.001), and ENPP2 and EZH2 protein expression also intensified (P<0.001); proliferation and invasiveness of HepG2.2.15 cells were obviously elevated compared to in HepG2 cells (P<0.01), while inhibition of ENPP2 or EZH2 expression in HepG2.2.15 cells greatly weakened proliferation and invasiveness of the cells (P<0.01). Conclusion The intensified expressions of ENPP2 and EZH2 in HepG2 cells and in HepG2.2.15 cells might play a pivotal role in carcinogenesis, which needs further investigation.

Key words: HepG2 cells, HepG2.2.15 cells, Ectonucleotide pyrophosphatase/phosphodiesterase 2, Enhancer of Zeste homolog 2, Proliferation, Invasion, In vitro

邓万玉, 黄子乐, 刘泽妍, 秦培毓, 刘娜. HepG2和HepG2.2.15细胞ENPP2/EZH2表达变化及其对细胞增殖和侵袭力的影响^*[J]. 实用肝脏病杂志, 2025, 28(4): 497-500.

Deng Wanyu, Huang Zile, Liu Zeyan, et al. Ectonucleotide pyrophosphatase/phosphodiesterase 2 and enhancer of Zeste homolog 2 in HepG2 and HepG2.2.15 cells and their impact on cell proliferation and invasiveness[J]. Journal of Practical Hepatology, 2025, 28(4): 497-500.

参考文献

[1] Elderkin J, Al Hallak N, Azmi AS, et al. Hepatocellular carcinoma: surveillance, diagnosis, evaluation and management. Cancers (Basel), 2023, 15(21): 5118.
[2] Song C, Lyu J, Liu Y, et al. Associations between hepatitis B virus infection and risk of all cancer types. JAMA Netw Open, 2019, 2(6): e195718.
[3] Borza R, Salgado-Polo F, Moolenaar WH, et al. Structure and function of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family: tidying up diversity. J Biol Chem, 2022, 298(2): 101526.
[4] Magkrioti C, Kaffe E, Aidinis V. The role of autotaxin and LPA signaling in embryonic development, pathophysiology and cancer. Int J Mol Sci, 2023, 24(9): 8325.
[5] Zeng J, Zhang J, Sun Y, et al. Targeting EZH2 for cancer therapy: from current progress to novel strategies. Eur J Med Chem, 2022, 238: 114419.
[6] Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers, 2021, 7(1): 6.
[7] Rizzo GEM, Cabibbo G, Craxi A. Hepatitis B virus-associated hepatocellular carcinoma. Viruses, 2022, 14(5): 986.
[8] Jiang Y, Han Q, Zhao H, et al. The mechanisms of HBV-induced hepatocellular carcinoma. J Hepatocell Carcin, 2021, 8: 435-450.
[9] 王可欣, 纪冬. 乙型肝炎病毒与肝细胞癌关系研究进展. 传染病信息, 2022, 35(2): 166-171.
[10] Chang JI, Sinn DH, Cho H, et al. Clinical outcomes of hepatitis B virus-related hepatocellular carcinoma patients with undetectable serum HBV DNA levels. Dig Dis Sci, 2022, 67(9): 4565-4573.
[11] Kim TS, Sinn DH, Kang W, et al. Hepatitis B virus DNA levels and overall survival in hepatitis B-related hepatocellular carcinoma patients with low-level viremia. J Gastroenterol Hepatol, 2019, 34(11): 2028-2035.
[12] Wang MD, Li C, Liang L, et al. Early and late recurrence of hepatitis B virus-associated hepatocellular carcinoma. Oncologist, 2020, 25(10): e1541-e1551.
[13] Liu Y, Kim ES, Guo H. Hepatitis B virus-related hepatocellular carcinoma exhibits distinct intratumoral microbiota and immune microenvironment signatures. J Med Virol, 2024, 96(2): e29485.
[14] Matas-Rico E, Frijlink E, van der Haar Avila I, et al. Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8(+) T cells. Cell Rep, 2021, 37(7): 110013.
[15] Meng J, Ruan X, Wei F, et al. High expression of ENPP2 is an independent predictor of poor prognosis in liver cancer. Medicine (Baltimore), 2023, 102(31): e34480.
[16] Kaffe E, Katsifa A, Xylourgidis N, et al. Hepatocyte autotaxin expression promotes liver fibrosis and cancer. Hepatology, 2017, 65(4): 1369-1383.
[17] Deng W, Chen F, Zhou Z, et al. Hepatitis B virus promotes hepatocellular carcinoma progression synergistically with hepatic stellate cells via facilitating the expression and secretion of ENPP2. Front Mol Biosci, 2021, 8: 745990.
[18] Ma YN, Wang SS, Liebe R, et al. Crosstalk between hepatic stellate cells and tumor cells in the development of hepatocellular carcinoma. Chin Med J (Engl), 2021, 134(21): 2544-2546.
[19] Myojin Y, Hikita H, Sugiyama M, et al. Hepatic stellate cells in hepatocellular carcinoma promote tumor growth via growth differentiation factor 15 production. Gastroenterology, 2021, 160(5): 1741-1754.
[20] Huang JL, Fu YP, Gan W, et al. Hepatic stellate cells promote the progression of hepatocellular carcinoma through microRNA-1246-RORα-Wnt/β-catenin axis. Cancer Lett, 2020, 476: 140-151.
[21] Ilango S, Paital B, Jayachandran P, et al. Epigenetic alterations in cancer. Front Biosci (Landmark Ed), 2020, 25(6): 1058-1109.
[22] Liu Y, Yang Q. The roles of EZH2 in cancer and its inhibitors. Med Oncol, 2023, 40(6): 167.
[23] Xu L, Lin J, Deng W, et al. EZH2 facilitates BMI1-dependent hepatocarcinogenesis through epigenetically silencing microRNA-200c. Oncogenesis, 2020, 9(11): 101.
[24] Chen F, Byrd AL, Liu J, et al. Polycomb deficiency drives a FOXP2-high aggressive state targetable by epigenetic inhibitors. Nat Commun, 2023, 14(1): 336.
[25] Yang X, Wan M, Yu F, et al. Histone methyltransferase EZH2 epigenetically affects CCNA1 expression in acute myeloid leukemia. Cell Signal, 2021, 87: 110144.

HepG2和HepG2.2.15细胞ENPP2/EZH2表达变化及其对细胞增殖和侵袭力的影响^*

Ectonucleotide pyrophosphatase/phosphodiesterase 2 and enhancer of Zeste homolog 2 in HepG2 and HepG2.2.15 cells and their impact on cell proliferation and invasiveness

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	李昂, 杨晓丹. DUSP10通过增强肝癌细胞干性促进对仑伐替尼耐药的实验研究^*[J]. 实用肝脏病杂志, 2025, 28(4): 493-496.
[2]	李全维, 高明慧, 寇卜心, 柴梦音, 霍云飞, 豆双双, 庞丽君, 石英, 刘晓霓. p65通过调控脂代谢影响HepG2细胞增殖研究^*[J]. 实用肝脏病杂志, 2025, 28(2): 173-177.
[3]	路瑶, 焦谊, 古丽阿依木. 利拉鲁肽通过Sirt1/AMPK信号通路改善肝细胞脂肪变性机制研究^*[J]. 实用肝脏病杂志, 2024, 27(5): 673-676.
[4]	杨丽花, 丁凌, 张玉明. PTBD联合体外辅助胆汁入肠治疗恶性梗阻性黄疸患者疗效研究^*[J]. 实用肝脏病杂志, 2024, 27(4): 619-622.
[5]	石影, 李亚妮, 李红刚. HepG2细胞Six4蛋白表达对细胞增殖、迁移和上皮-间充质转化的影响[J]. 实用肝脏病杂志, 2024, 27(4): 635-637.
[6]	吴伟杰, 丁雯瑾, 杨蕊旭, 范建高. Notch抑制剂DAPT体外改善L02细胞脂肪变研究^*[J]. 实用肝脏病杂志, 2024, 27(1): 16-19.
[7]	仲金龙, 施琳. miR-556-3p通过调控PTEN/AKT信号通路影响肝细胞癌的转移活性^*[J]. 实用肝脏病杂志, 2023, 26(6): 781-784.
[8]	霍云飞, 寇卜心, 柴梦音, 豆双双, 高明慧, 石英, 刘晓霓. 体外靶向TP53BP2基因shRNA慢病毒载体的构建及功能鉴定^*[J]. 实用肝脏病杂志, 2023, 26(2): 164-168.
[9]	孙东磊, 郭金波, 王丹丹, 罗雨欣, 牛国超, 杨双双, 张晓岚. 间充质干细胞外泌体对体外肝星状细胞增殖和活化的影响[J]. 实用肝脏病杂志, 2023, 26(1): 11-14.
[10]	贺潇瑾, 李丹, 周青, 欧阳静, 田玉球, 谭英征. L02细胞乙型肝炎病毒X蛋白和SOCS-1基因水平研究^*[J]. 实用肝脏病杂志, 2022, 25(6): 772-775.
[11]	胡鹏蕴, 赵宏峰, 杨小伟, 史保宾. 新型促癌基因LSM11通过Wnt/β-catenin信号通路促进肝癌细胞增殖^*[J]. 实用肝脏病杂志, 2022, 25(5): 628-632.
[12]	任洁雯, 李宗怡, 任嘉欣, 赖鸣杰. 大花旋覆花素对体外Hep G2细胞增殖、凋亡和mTORC1信号通路的影响^*[J]. 实用肝脏病杂志, 2022, 25(4): 468-471.
[13]	白亮, 王宝太, 高志峰, 蒋安, 梁金强. PAX6通过MEK/ERK信号通路抑制肝星状细胞活化和增殖实验研究[J]. 实用肝脏病杂志, 2022, 25(3): 318-322.
[14]	何亚娟, 王飞, 姚耐娟, 吴宇超, 田臻. 乙型肝炎病毒全x蛋白体外诱导肝星状细胞炎症反应并促进肝细胞凋亡^*[J]. 实用肝脏病杂志, 2022, 25(3): 323-326.
[15]	刘文竹, 胡欣, 江伟, 左秀静, 朱华军. 小泛素样修饰物特异性蛋白酶3通过调节脂滴水平体外促进HepG2细胞丙型肝炎病毒复制[J]. 实用肝脏病杂志, 2022, 25(2): 161-164.