CircCRIM1 Promotes Hepatocellular Carcinoma Proliferation and Angiogenesis by Sponging miR-378a-3p and Regulating SKP2 Expression

被引:26
|
作者
Ji, Yang [1 ]
Yang, Shikun [1 ]
Yan, Xueqi [2 ]
Zhu, Li [3 ]
Yang, Wenjie [1 ]
Yang, Xinchen [1 ]
Yu, Fei [1 ]
Shi, Longqing [3 ]
Zhu, Xi [4 ]
Lu, Yunjie [3 ]
Zhang, Chuanyong [1 ]
Lu, Hao [1 ]
Zhang, Feng [1 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 1, Hepatobiliary Liver Transplantat Ctr, Key Lab Liver Transplantat,Chinese Acad Med Sci, Nanjing, Peoples R China
[2] Nanjing Med Univ, Affiliated Hosp 1, Dept Oncol, Nanjing, Peoples R China
[3] Soochow Univ, Hosp 3, Dept Hepatobiliary Surg, Changzhou, Jiangsu, Peoples R China
[4] Jiangsu Univ, Peoples Hosp Kunshan 1, Dept Infect Dis, Zhenjiang, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
circCRIM1; HCC; MiR-378a-3p; Skp2; proliferation; angiogenesis; TARGET PREDICTION; SURVIVAL; GENE;
D O I
10.3389/fcell.2021.796686
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Mounting evidence has demonstrated that circular RNAs have an important function in tumorigenesis and cancer evolvement. CircCRIM1 has been shown to be a poor prognostic element in multiple human malignancies. However, the clinical significance and mechanism of circCRIM1 in hepatocellular carcinoma (HCC) is still unclear. The present study confirmed the expression level of circCRIM1 using quantitative real-time PCR. In addition, circCRIM1 siRNA and overexpression vectors were used for transfection into LM3 or Huh7 cells to down- or up-regulate the expression of circCRIM1. In vitro and in vivo experiments were performed to explore the function of circCRIM1 in HCC. RNA pull-down, RNA immunoprecipitation, fluorescent in situ hybridization, and luciferase reporter assays were conducted to confirm the relationship between miR-378a-3p and circCRIM1 or S-phase kinase-associated protein 2 (SKP2) in HCC. Then, circCRIM1 was up-regulated in HCC and its expression level was significantly associated with poor prognosis and clinicopathologic characteristics. CircCRIM1 enhanced the proliferation and angiogenesis of HCC cells in vitro and promoted xenograft growth in vivo. Moreover, circCRIM1 upregulated the expression of SKP2 by functioning as a sponge for miR-378a-3p. These findings suggest that circCRIM1 boosts the HCC progression via the miR-378-3p/SKP2 axis and may act as a crucial epigenetic therapeutic molecule target in HCC.
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页数:16
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