Curcumin restrains hepatocellular carcinoma progression depending on the regulation of the circ_0078710/miR-378b/PRIM2 axis

姜黄素 基因敲除 基因沉默 化学 分子生物学 流式细胞术 小干扰RNA 癌症研究 细胞凋亡 体内 小RNA 生物 核糖核酸 生物化学 基因 生物技术
作者
Qian Chen,Hai Guo,Yan Zong,Xiaofeng Zhao
出处
期刊:Journal of Receptors and Signal Transduction [Taylor & Francis]
卷期号:42 (3): 313-324 被引量:20
标识
DOI:10.1080/10799893.2021.1936554
摘要

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).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.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.Circ_0078710 silencing aggravated curcumin-mediated anti-tumor effects through mediating the miR-378b/PRIM2 signaling in HCC cells.
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