[1]彭强,王健宇,何承峻,等.circATP8A1在肝癌中的表达及沉默其表达对肝癌细胞增殖和迁移的作用实验研究[J].陕西医学杂志,2026,(6):742-747.[doi:DOI:10.3969/j.issn.1000-7377.2026.06.004]
　PENG Qiang,WANG Jianyu,HE Chengjun,et al.Expression of circATP8A1 in hepatocellular carcinoma and mechanism of silencing its expression on proliferation and migration of hepatocellular carcinoma cells[J].,2026,(6):742-747.[doi:DOI:10.3969/j.issn.1000-7377.2026.06.004]
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circATP8A1在肝癌中的表达及沉默其表达对肝癌细胞增殖和迁移的作用实验研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年6期
页码:
742-747
栏目:
基础研究
出版日期:
2026-06-05

文章信息/Info

Title:
Expression of circATP8A1 in hepatocellular carcinoma and mechanism of silencing its expression on proliferation and migration of hepatocellular carcinoma cells
作者:
彭强1; 王健宇1; 何承峻1; 陈海洋1; 陈志强2; 王一君3（荷兰）
（1.四川大学华西医院资阳医院 资阳市中心医院肝胆胰外科，四川 资阳 641300；2.南京医科大学第一附属医院肿瘤科，江苏 南京 210036；3.荷兰癌症研究所，荷兰 阿姆斯特丹 1066CX）
Author(s):
PENG Qiang1; WANG Jianyu1; HE Chengjun1; CHEN Haiyang1; CHEN Zhiqiang2; WANG Yijun3
(1.Department of Hepatobiliary and Pancreatic Surgery，Ziyang Central Hospital，West China Hospital，Sichuan University，Ziyang 641300，China;2.Department of Oncology，the First Affiliated Hospital of Nanjing Medical University，Nanjing 210036，China;3.Netherlands Cancer Institute，Amsterdam 1066CX，Netherlands)
关键词:
肝癌; 环状RNA; circATP8A1; 微小RNA-199a-5p; 增殖; 迁移
Keywords:
Hepatocellular carcinoma; Circular RNA; circATP8A1; miR-199a-5p; Proliferation; Migration
分类号:
R 735.7
DOI:
DOI:10.3969/j.issn.1000-7377.2026.06.004
文献标志码:
A
摘要:
目的：探讨沉默环状RNA（circRNA）circATP8A1通过靶向微小RNA（miR）-199a-5p对肝癌细胞增殖、迁移的作用。方法：OncoMine数据库分析肝癌组织中circATP8A1的表达及circATP8A1表达与肝癌患者生存期的关系。实时荧光定量PCR（RT-qPCR）检测肝癌细胞系（QGY-7701、Huh-7、SMMC-7721、HepG2、MHCC97H）中circATP8A1的表达。分别将si-NC和si-circATP8A1序列转染HepG2细胞，定义为si-NC组和si-circATP8A1组。克隆形成实验和划痕愈合实验检测各组HepG2细胞增殖和迁移能力。Western blot检测各组HepG2细胞中增殖表型蛋白髓细胞瘤癌基因（c-myc）、增殖细胞核抗原（PCNA）和迁移表型蛋白基质金属蛋白酶-2（MMP-2）、MMP-9表达。双荧光素酶报告基因实验验证circATP8A1与miR-199a-5p的靶向关系。OncoMine数据库分析肝癌组织中circATP8A1和miR-199a-5p表达的相关性。RT-qPCR检测各组HepG2细胞中miR-199a-5p的表达。结果：肝癌组织中circATP8A1表达明显高于正常肝组织（P<0.01）。circATP8A1低表达的肝癌患者生存期明显长于circATP8A1高表达的肝癌患者（P<0.01）。与正常肝LO2细胞比较，QGY-7701、Huh-7、SMMC-7721、HepG2、MHCC97H细胞中circATP8A1表达升高（均P<0.01）。与si-NC组比较，si-circATP8A1组HepG2细胞的克隆形成数降低，细胞划痕愈合率降低，细胞中c-myc、PCNA、MMP-2和MMP-9蛋白表达降低（均P<0.01）。circATP8A1能够靶向结合miR-199a-5p。肝癌组织中circATP8A1与miR-199a-5p表达呈负相关（P<0.01）。si-circATP8A1组HepG2细胞miR-199a-5p表达高于si-NC组（P<0.01）。结论：沉默circATP8A1通过靶向上调miR-199a-5p表达抑制肝癌HepG2细胞增殖和迁移能力。
Abstract:
Objective:To investigate the effects of silencing circular RNA (circRNA) circATP8A1 on the proliferation and migration of hepatocellular carcinoma cells by targeting microRNA (miR)-199a-5p.Methods：The OncoMine database was used to analyze the expression of circATP8A1 in liver cancer tissues and the relationship between circATP8A1 expression and survival in liver cancer patients.RT-qPCR was used to detect circATP8A1 expression in liver cancer cell lines (QGY-7701，Huh-7，SMMC-7721，HepG2，and MHCC97H).HepG2 cells were transfected with si-NC and si-circATP8A1 sequences，respectively，defining the si-NC and si-circATP8A1 groups.Colony formation assays and wound healing assays were used to assess the proliferation and migration abilities of HepG2 cells in each group.Western blot was used to detect the expression of proliferative phenotype proteins c-myc and proliferating cell nuclear antigen (PCNA)，as well as migratory phenotype proteins matrix metalloproteinase-2 (MMP-2) and MMP-9 in HepG2 cells from each group.Dual-luciferase reporter assays were used to verify the targeting relationship between circATP8A1 and miR-199a-5p.The OncoMine database was used to analyze the correlation between circATP8A1 and miR-199a-5p expression in hepatocellular carcinoma tissues.RT-qPCR was used to detect the expression of miR-199a-5p in HepG2 cells from each group.Results:Expression of circATP8A1 was significantly higher in liver cancer tissues than that in normal liver tissues (P<0.01).Hepatocellular carcinoma patients with low circATP8A1 expression had significantly longer survival than those with high circATP8A1 expression (P<0.01).Compared with normal liver LO2 cells，circATP8A1 expression was elevated in QGY-7701，Huh-7，SMMC-7721，HepG2，and MHCC97H cells (all P<0.01).Compared with the si-NC group，the si-circATP8A1 group showed decreased colony formation in HepG2 cells，decreased wound healing rate，and decreased expression of c-myc，PCNA，MMP-2，and MMP-9 proteins (all P<0.01).circATP8A1 could target and bind to miR-199a-5p.The expression of circATP8A1 was negatively correlated with miR-199a-5p in liver cancer tissues (P<0.01).Compared with the si-NC group，the expression of miR-199a-5p in HepG2 cells in the si-circATP8A1 group was increased (P<0.01).Conclusion:Silencing circATP8A1 inhibits the proliferation and migration of HepG2 liver cancer cells by targeting and upregulating miR-199a-5p expression.

参考文献/References:

[1]ZHONG B Y，FAN W，GUAN J J，et al.Combination locoregional and systemic therapies in hepatocellular carcinoma[J].Lancet Gastroenterol Hepatol，2025，10(4)：369-386.[2]YANG Y，CHEN X Q，JIA Y X，et al.Circ-0044539 promotes lymph node metastasis of hepatocellular carcinoma through exosomal-miR-29a-3p[J].Cell Death Dis，2024，15(8)：630.[3]GUO J，LIANG R，CHUNG A，et al.The origin of hepatocellular carcinoma depends on metabolic zonation[J].Science，2026，391(6784)：7129.[4]LLOVET J M，WILLOUGHBY C E，SINGAL A G，et al.Nonalcoholic steatohepatitis-related hepatocellular carcinoma：pathogenesis and treatment[J].Nat Rev Gastroenterol Hepatol，2023，20(8)：487-503.[5]GUO Z，LI Z，GUO J，et al.A N7-methylguanosine modified circular RNA，circIPP2A2，promotes malignant behaviors in hepatocellular carcinoma by serving as a scaffold in modulating the Hornerin/PI3K/AKT/GSK3β axis[J].Cell Death Dis，2024，15(11)：868.[6]刘毅力，郭冲，尹恒，等.环状RNA circ-TAGLN在卵巢癌细胞中的表达及对卵巢癌细胞增殖和侵袭的影响[J].陕西医学杂志，2024，53(2)：147-151.[7]XIA J，ZHAO H，EDMONDSON J L，et al.Role of NEK2 in tumorigenesis and tumor progression[J].Trends Mol Med，2025，31(1)：79-93.[8]JI Y，NI C，SHEN Y，et al.ESRP1-mediated biogenesis of circPTPN12 inhibits hepatocellular carcinoma progression by PDLIM2/NF-κB pathway[J].Mol Cancer，2024，23(1)：143.[9]ZHAO L，YUAN H，WANG Y，et al.p-STAT3-elevated E3 ubiquitin ligase DTX4 confers the stability of HBV cccDNA by ubiquitinating APOBEC3B in liver[J].Theranostics，2024，14(15)：6036-6052.[10]TESTONI B，SCHOLTS C，PLISSONNIER M L，et al.Quantification of circulating HBV RNA expressed from intrahepatic cccDNA in untreated and NUC treated patients with chronic hepatitis B[J].Gut，2024，73(4)：659-667.[11]DENG C，HUO M，CHU H，et al.Exosome circATP8A1 induces macrophage M2 polarization by regulating the miR-1-3p/STAT6 axis to promote gastric cancer progression[J].Mol Cancer，2024，23(1)：49.[12]ZHOU L，ZHANG Q，CHENG J，et al.LncRNA SNHG1 upregulates FANCD2 and G6PD to suppress ferroptosis by sponging miR-199a-5p/3p in hepatocellular carcinoma[J].Drug Discov Ther，2023，17(4)：248-256.[13]易三凤，屈银宗，龚承先，等.环状RNA GRIN2B通过调控微小RNA-135b对食管癌细胞增殖和侵袭的影响实验研究[J].陕西医学杂志，2024，53(3)：308-312.[14]ZHANG X Y，LI S S，GU Y R，et al.CircPIAS1 promotes hepatocellular carcinoma progression by inhibiting ferroptosis via the miR-455-3p/NUPR1/FTH1 axis[J].Mol Cancer，2024，23(1)：113.[15]ZHOU J，SONG Q，LI H，et al.Targeting circ-0034880-enriched tumor extracellular vesicles to impede SPP1(high)CD206(+) pro-tumor macrophages mediated pre-metastatic niche formation in colorectal cancer liver metastasis[J].Mol Cancer，2024，23(1)：168.[16]ZHU X，ZHANG P.m6A-modified circXPO1 accelerates colorectal cancer progression via interaction with FMRP to promote WWC2 mRNA decay[J].J Transl Med，2024，22(1)：931.[17]ZHANG Y，YAO R，LI M，et al.CircTTC13 promotes sorafenib resistance in hepatocellular carcinoma through the inhibition of ferroptosis by targeting the miR-513a-5p/SLC7A11 axis[J].Mol Cancer，2025，24(1)：32.[18]LI H，SU B，JIANG Y，et al.Circular RNA circDCUN1D4 suppresses hepatocellular carcinoma development via targeting the miR-590-5p/ TIMP3 axis[J].Mol Cancer，2025，24(1)：95.[19]LI J，WANG X，SHI L，et al.A mammalian conserved circular RNA CircLARP1B regulates hepatocellular carcinoma metastasis and lipid metabolism[J].Adv Sci (Weinh)，2024，11(2)：e2305902.[20]CHEN L，XIAO H，WU Y，et al.CircPHKB decreases the sensitivity of liver cancer cells to sorafenib via miR-1234-3p/CYP2W1 axis[J].Genomics，2024，116(1)：110764.[21]CHEN R X，LIU S C，KAN X C，et al.CircUGP2 suppresses intrahepatic cholangiocarcinoma progression via p53 signaling through interacting with PURB to regulate ADGRB1 transcription and sponging miR-3191-5p[J].Adv Sci (Weinh)，2024，11(38)：e2402329.[22]FEI D，WANG F，WANG Y，et al.Circular RNA ACVR2A promotes the progression of hepatocellular carcinoma through mir-511-5p targeting PI3K-Akt signaling pathway[J].Mol Cancer，2024，23(1)：159.[23]LIU X，WANG X，CHAI B，et al.MiR-199a-3p/5p regulate tumorgenesis via targeting Rheb in non-small cell lung cancer[J].Int J Biol Sci，2022，18(10)：4187-4202.[24]MING F，LI B，YI S，et al.Circ_0087378 intensifies the malignant behavior of non-small cell lung cancer cells in vitro by facilitating DDR1 via sponging miR-199a-5p[J].Transl Lung Cancer Res，2023，12(4)：770-785.[25]PHATAK P，TULAPURKAR M E，BURROWS W M，et al.MiR-199a-5p decreases esophageal cancer cell proliferation partially through repression of Jun-B[J].Cancers (Basel)，2023，15(19)：4811.

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备注/Memo

备注/Memo:
国家自然科学基金资助项目（82002556）
更新日期/Last Update: 2026-06-05