Page 43 - 南京医科大学学报自然科学版

第41卷第3期 南京医科大学学报（自然科学版）
2021年3月 Journal of Nanjing Medical University（Natural Sciences） ·349 ·

·基础研究·

miR⁃202及其靶基因Glypican⁃3在肝癌中的表达及其临床意义

周肖英 ，林 彬 ，侯云华 ，司淑平 2
1
1
1
江苏联合职业技术学院无锡卫生分院护理系，江苏 无锡 214028；南京医科大学附属无锡人民医院消化内科，江苏 无
1 2
锡 214000

［摘 要］ 目的：探究肝癌标志物磷脂酰肌醇蛋白聚糖3（glypican⁃3，GPC3）与miR⁃202相互调控的分子机制。方法：取126例
临床肝癌组织标本及血清样本，免疫组化检测GPC3表达，qRT⁃PCR检测循环miR⁃202的水平；培养肝癌HepG2细胞，转染miR
⁃202 mimics，qRT⁃PCR检测miR⁃202表达，Western blot检测GPC3表达；CCK8实验检测miR⁃202 mimics对HepG2细胞增殖活性
的影响；Luciferase 报告基因实验检测miR⁃202对GPC3的调控。结果：临床126例肝癌GPC3总阳性率为77.78%，其表达水平
与患者性别、年龄、肿瘤大小、临床分期无关，但与细胞组织学分化类型以及微血管侵犯高度相关。肝癌患者循环miR⁃202呈
低水平状态，且与癌组织GPC3表达水平呈负相关关系。上调HepG2细胞中miR⁃202表达，GPC3表达随之下调，且癌细胞增殖
受抑制。Luciferase实验证实miR⁃202可直接负调控GPC3的表达。结论：GPC3受miR⁃202的直接调控，GPC3高表达与肝癌恶
性生物学表征密切相关。靶向GPC3的治疗策略如能辅助提高miR⁃202的功能，将可能产生协同抗肝癌的效果。
［关键词］ 肝癌；循环miR⁃202；glypican⁃3；靶向治疗；作用机制
［中图分类号］ R735.7 ［文献标志码］ A ［文章编号］ 1007⁃4368（2021）03⁃349⁃06
doi：10.7655/NYDXBNS20210307

Expression and clinical significance of miR ⁃ 202 and its target gene glypican ⁃ 3 in

hepatocellular carcinoma
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1
ZHOU Xiaoying ，LIN bin ，HOU Yuhua ，SI Shuping 2
Department of Nursing，Wuxi Branch of Jiangsu Union Technical Institute，Wuxi 214028；Department of
1 2
Gastroenterology，Wuxi People’s Hospital Affiliated to Nanjing Medical University，Wuxi 214000，China
［Abstract］ Objective： This study aims to explore the molecular mechanism of the interaction between hepatocellular carcinoma
（HCC）markers of glypican⁃3（GPC3）and miR⁃202. Methods：Total 126 cases of clinical HCC tissue samples and serum samples were
collected. The expression of GPC3 was detected by immunohistochemistry，and the level of circulating miR⁃202 was detected by qRT⁃
PCR. The HepG2 cells were cultured and transfected with miR⁃202 mimics，the expression of miR⁃202 was detected by qRT⁃PCR，and
the expression of GPC3 protein was detected by Western blot. The effect of miR⁃202 mimics on the proliferation activity of HepG2 cells
was detected by CCK8 assay. Luciferase reporter gene was used to determine the regulation of miR⁃202 on GPC3. Results：The total
positive rate of GPC3 in 126 cases of HCC was 77.78%. Its expression level was not related to the patient’s gender，age，tumor size and
clinical stage，but was highly correlated with the type of histological differentiation and microvascular invasion. The circulating miR⁃
202 in HCC patients was at a low level，and was inversely correlated with the expression level of GPC3 in cancer tissues. The
expression of miR ⁃ 202 was up ⁃ regulated in HepG2 cells，and the expression of GPC3 was down ⁃ regulated accordingly，and the
proliferation activity of cancer cells was thus inhibited. Luciferase experiment confirmed that miR⁃ 202 could directly and negatively
regulate the expression of GPC3. Conclusion：This study demonstrates that GPC3 is directly regulated by miR ⁃ 202，and high
expression of GPC3 is a sign of malignant biological feature of HCC. Any targeted GPC3 therapeutic strategy，if it can assist to improve
the function of miR⁃202，may produce a synergistic anti⁃tumor effect for HCC.
［Key words］ hepatocellular carcinoma；circulating miR⁃202；glypican⁃3；targeted therapy；mechanism
［J Nanjing Med Univ，2021，41（03）：349⁃354］