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.
引用
收藏
页码:313 / 324
页数:12
相关论文
共 41 条
[1]   Curcumin: a unique antioxidant offers a multimechanistic approach for management of hepatocellular carcinoma in rat model [J].
Ahmed, Hanaa H. ;
Shousha, Wafaa Gh. ;
Shalby, Aziza B. ;
El-Mezayen, Hatem A. ;
Ismaiel, Nora N. ;
Mahmoud, Nadia S. .
TUMOR BIOLOGY, 2015, 36 (03) :1667-1678
[2]   Novel carbocyclic curcumin analog CUR3d modulates genes involved in multiple apoptosis pathways in human hepatocellular carcinoma cells [J].
Bhullar, Khushwant S. ;
Jha, Amitabh ;
Rupasinghe, H. P. Vasantha .
CHEMICO-BIOLOGICAL INTERACTIONS, 2015, 242 :107-122
[3]   Curcumin and tumor immune-editing: resurrecting the immune system [J].
Bose, Sayantan ;
Panda, Abir Kumar ;
Mukherjee, Shravanti ;
Sa, Gaurisankar .
CELL DIVISION, 2015, 10
[4]   miR-187-3p inhibits the metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting S100A4 [J].
Dou, Changwei ;
Liu, Zhikui ;
Xu, Meng ;
Jia, Yuli ;
Wang, Yufeng ;
Li, Qing ;
Yang, Wei ;
Zheng, Xin ;
Tu, Kangsheng ;
Liu, Qingguang .
CANCER LETTERS, 2016, 381 (02) :380-390
[5]   Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis [J].
El-Serag, Hashem B. ;
Rudolph, Lenhard .
GASTROENTEROLOGY, 2007, 132 (07) :2557-2576
[6]   Curcumin and Cancer [J].
Giordano, Antonio ;
Tommonaro, Giuseppina .
NUTRIENTS, 2019, 11 (10)
[7]   Changing epidemiology of hepatocellular carcinoma in Asia [J].
Goh, George Boon-Bee ;
Chang, Pik-Eu ;
Tan, Chee-Kiat .
BEST PRACTICE & RESEARCH CLINICAL GASTROENTEROLOGY, 2015, 29 (06) :919-928
[8]   Natural RNA circles function as efficient microRNA sponges [J].
Hansen, Thomas B. ;
Jensen, Trine I. ;
Clausen, Bettina H. ;
Bramsen, Jesper B. ;
Finsen, Bente ;
Damgaard, Christian K. ;
Kjems, Jorgen .
NATURE, 2013, 495 (7441) :384-388
[9]   CircRNA hsa_circRNA_104348 promotes hepatocellular carcinoma progression through modulating miR-187-3p/RTKN2 axis and activating Wnt/β-catenin pathway [J].
Huang, Guanqun ;
Liang, Min ;
Liu, Haiyan ;
Huang, Jianhong ;
Li, Peiqing ;
Wang, Chong ;
Zhang, Yidan ;
Lin, Ye ;
Jiang, Xianhan .
CELL DEATH & DISEASE, 2020, 11 (12)
[10]   MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression [J].
Hyun, Jeongeun ;
Wang, Sihyung ;
Kim, Jieun ;
Rao, Kummara Madhusudana ;
Park, Soo Yong ;
Chung, Ildoo ;
Ha, Chang-Sik ;
Kim, Sang-Woo ;
Yun, Yang H. ;
Jung, Youngmi .
NATURE COMMUNICATIONS, 2016, 7