CircZNF609 enhances hepatocellular carcinoma cell proliferation, metastasis, and stemness by activating the Hedgehog pathway through the regulation of miR-15a-5p/15b-5p and GLI2 expressions
机构：[1]Cancer Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, 610072 Chengdu, Sichuan, China.四川省人民医院[2]Cancer Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, 611731 Chengdu, China.四川省人民医院[3]Department of Radiotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, 55# Renmin South Road, 610041 Chengdu, Sichuan, China.四川省人民医院四川省肿瘤医院[4]Department of Burn and Plastic Surgery, Affiliated hospital of Chengdu Medical College, 610000 Chengdu, Sichuan, China.[5]Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pujian Road, Pudong New District, 200127 Shanghai, China.[6]Department of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research, No. 42 Baiziting Road, Xuanwu District, 210009 Nanjing, China.[7]Department of Medical Oncology, the First Affiliated Hospital of Soochow University, No.188, Shizi Street, Gusu District, 215006 Suzhou, Jiangsu, China.[8]Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Gusu District, 215006 Suzhou, Jiangsu, China
Emerging evidence has revealed that aberrantly expressed circular RNAs (circRNAs) play vital roles in tumorigenesis and progression of diverse human malignancies. Although an existing literature has elucidated the regulatory role of circZNF609 in breast cancer, the crucial function that circZNF609 exerted on hepatocellular carcinoma (HCC) remains unclear. Herein, we determined to explore the molecular mechanism of circZNF609 in HCC. In this study, circZNF609 was conspicuously overexpressed and featured with loop structure in HCC. Functional tests revealed that decreased expression of circZNF609 suppressed cell proliferation, metastasis and stemness, whereas induced cell apoptosis in HCC. Subsequent molecular mechanism assays indicated that circZNF609 contributed to HCC progression through activation of Hedgehog pathway. Moreover, circZNF609 was found to be negatively correlated with miR-15a-5p/15b-5p but positively correlated with GLI2. Moreover, there was a negative correlation between miR-15a-5p/15b-5p and GLI2. Rescue experiments testified that GLI2 overexpression could recover circZNF609 depletion-mediated function on HCC development while miR-15a-5p/15b-5p inhibition could partially rescue circZNF609 silencing-mediated effect on HCC progression. Final experiments in vivo further elucidated the suppressive function of circZNF609 knockdown on the tumorigenesis of HCC. Briefly, circZNF609 enhances HCC cell proliferation, metastasis, and stemness by activating the Hedgehog pathway through the regulation of miR-15a-5p/15b-5p and GLI2 expressions.
基金：
This work was
supported by the National Natural Science Foundation of China (No. 81972815
and 81672928), Financial Grant from the China Postdoctoral Science
Foundation (No. 2018T110466 and 2017M621678) and Suzhou Science and
Technology Bureau Project (No. SYS2019036).
第一作者机构：[1]Cancer Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, 610072 Chengdu, Sichuan, China.[2]Cancer Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, 611731 Chengdu, China.
共同第一作者：
通讯作者：
通讯机构：[5]Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pujian Road, Pudong New District, 200127 Shanghai, China.[6]Department of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research, No. 42 Baiziting Road, Xuanwu District, 210009 Nanjing, China.[7]Department of Medical Oncology, the First Affiliated Hospital of Soochow University, No.188, Shizi Street, Gusu District, 215006 Suzhou, Jiangsu, China.
推荐引用方式(GB/T 7714)：
Yangke He,Hui Huang,Li Jin,et al.CircZNF609 enhances hepatocellular carcinoma cell proliferation, metastasis, and stemness by activating the Hedgehog pathway through the regulation of miR-15a-5p/15b-5p and GLI2 expressions[J].CELL DEATH & DISEASE.2020,11(5):doi:10.1038/s41419-020-2441-0.
APA：
Yangke He,Hui Huang,Li Jin,Fang Zhang,Ming Zeng...&Wansheng Wang.(2020).CircZNF609 enhances hepatocellular carcinoma cell proliferation, metastasis, and stemness by activating the Hedgehog pathway through the regulation of miR-15a-5p/15b-5p and GLI2 expressions.CELL DEATH & DISEASE,11,(5)
MLA：
Yangke He,et al."CircZNF609 enhances hepatocellular carcinoma cell proliferation, metastasis, and stemness by activating the Hedgehog pathway through the regulation of miR-15a-5p/15b-5p and GLI2 expressions".CELL DEATH & DISEASE 11..5(2020)
生物学