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Curcumin restrains hepatocellular carcinoma progression depending on the regulation of the circ_0078710/miR-378b/PRIM2 axis
被引:26
作者:
Chen, Qian
[1
]
Guo, Hai
[1
]
Zong, Yan
[1
]
Zhao, Xiaofeng
[1
]
机构:
[1] Nanjing Med Univ, Dept Tradit Chinese Med, Affiliated Huaian Peoples Hosp 1, 1 Huanghe West Rd, Huaian City 223300, Jiangsu, Peoples R China
关键词:
Hepatocellular carcinoma;
curcumin;
circ_0078710;
miR-378b;
PRIM2;
CELL-PROLIFERATION;
SUPPRESSES PROLIFERATION;
LIVER-CANCER;
METASTASIS;
GENES;
TUMORIGENESIS;
EPIDEMIOLOGY;
REPLICATION;
APOPTOSIS;
SUBUNIT;
D O I:
10.1080/10799893.2021.1936554
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Purpose Curcumin has shown anti-tumor activity in multiple malignancies. The aim of our study was to explore the molecular mechanism behind the anti-tumor activity of curcumin in hepatocellular carcinoma (HCC). Methods The proliferation, migration, invasion, and apoptosis were analyzed by 5-ethynyl-2 '-deoxyuridine (EDU) assay, transwell migration assay, transwell invasion assay, and flow cytometry. Western blot assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were conducted to analyze protein and RNA expression. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA-pull down assay were performed to confirm the interaction between microRNA-378b (miR-378b) and circular RNA_0078710 (circ_0078710) or DNA primase, polypeptide 2 (PRIM2). Tumor xenograft assay was conducted to assess the roles of curcumin and circ_0078710 in vivo. Results Curcumin stimulation restrained the proliferation, migration, and invasion, and triggered the apoptosis of HCC cells. Curcumin down-regulated the expression of circ_0078710 in HCC cells in a dose-dependent manner. Circ_0078710 knockdown aggravated curcumin-mediated anti-tumor effects in HCC cells. Circ_0078710 acted as a molecular sponge for miR-378b. Circ_0078710 interference-induced effects in curcumin-stimulated HCC cells were partly abolished by the silence of miR-378b. MiR-378b bound to the 3 ' untranslated region (3 ' UTR) of PRIM2. PRIM2 overexpression partly reversed circ_0078710 interference-mediated influences in curcumin-treated HCC cells. Circ_0078710 silencing aggravated curcumin-mediated suppressive effect in tumor growth in vivo. Conclusions Circ_0078710 silencing aggravated curcumin-mediated anti-tumor effects through mediating the miR-378b/PRIM2 signaling in HCC cells.
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页码:313 / 324
页数:12
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