CircUBAP2 Promotes MMP9-Mediated Oncogenic Effect via Sponging miR-194-3p in Hepatocellular Carcinoma

Boqiang Liu; Yuanshi Tian; Mingyu Chen; Hao Shen; Jiafeng Xia; Junjie Nan; Tingting Yan; Yifan Wang; Yifan Wang; Liang Shi; Liang Shi; Bo Shen; Hong Yu; Xiujun Cai; Xiujun Cai; Xiujun Cai; Xiujun Cai; Xiujun Cai

doi:10.3389/fcell.2021.675043

Frontiers in Cell and Developmental Biology (Jun 2021)

CircUBAP2 Promotes MMP9-Mediated Oncogenic Effect via Sponging miR-194-3p in Hepatocellular Carcinoma

Boqiang Liu,
Yuanshi Tian,
Mingyu Chen,
Hao Shen,
Jiafeng Xia,
Junjie Nan,
Tingting Yan,
Yifan Wang,
Yifan Wang,
Liang Shi,
Liang Shi,
Bo Shen,
Hong Yu,
Xiujun Cai,
Xiujun Cai,
Xiujun Cai,
Xiujun Cai,
Xiujun Cai

Affiliations

Boqiang Liu: Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Yuanshi Tian: Department of Diagnostic Ultrasound and Echocardiography, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Mingyu Chen: Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Hao Shen: Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Jiafeng Xia: State Key Laboratory for Diagnosis, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Junjie Nan: Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Tingting Yan: Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Yifan Wang: Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Yifan Wang: Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Liang Shi: Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Liang Shi: Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Bo Shen: Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Hong Yu: Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Xiujun Cai: Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Xiujun Cai: Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Xiujun Cai: Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang University, Hangzhou, China
Xiujun Cai: Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, Zhejiang University, Hangzhou, China
Xiujun Cai: Zhejiang University Cancer Center, Zhejiang University, Hangzhou, China

DOI: https://doi.org/10.3389/fcell.2021.675043
Journal volume & issue: Vol. 9

Abstract

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BackgroundThe physiological regulatory functions of circRNAs have become a topic of intensive research in recent years. Increasing evidence supports a significant role of circRNAs during cancer initiation and progression, including hepatocellular carcinoma (HCC).Materials and MethodsA bioinformatics analysis from three independent Gene Expression Omnibus (GEO) databases was performed to profile and screen the dysregulated circRNAs in HCC. RT-qPCR was used to examine the expression level of circUBAP2 in HCC and adjacent non-tumor tissues. Then, proliferation assays (CCK8 and colony formation) and migration assays (transwell and wound healing) were performed to examine effect of circUBAP2 in vitro. Immunoprecipitation, RNA pulldown, FISH, and dual-luciferase reporter assay was conducted to explore the circUBAP2-related mechanism for regulating HCC progression. Moreover, a mouse xenograft model and a mouse lung metastasis model confirmed the effect of circUBAP2 in vivo.ResultsIn this study, we found a novel circRNA: circUBAP2, which was identified by bioinformatics analysis. Among 91 HCC patients, circUBAP2 was significantly upregulated in HCC tissues, and negatively correlated with aggressive clinical characteristics and prognosis. Functional assays demonstrated that circUBAP2 promoted cell proliferation, colony formation, migration, and invasion in vitro. Moreover, circUBAP2 enhanced tumor growth and pulmonary metastasis in vivo. Mechanistically, circUBAP2 acts as a competing endogenous RNA (ceRNA) for miR-194-3p, a tumor suppressor in HCC. We confirmed that MMP9 was direct target for miR-194-3p, which was regulated by circUBAP2.ConclusionCircUBAP2 plays a significant role in promoting HCC via the miR-194-3p/MMP9 pathway and could serve as a promising prognostic biomarker and novel therapeutic target for HCC patients.

Published in Frontiers in Cell and Developmental Biology

ISSN: 2296-634X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.frontiersin.org/journals/cell-and-developmental-biology

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