期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 -, 期 -, 页码 -出版社
WILEY
DOI: 10.1111/jcmm.15010
关键词
competing endogenous RNA; haematopoietic- and neurologic-expressed sequence 1; hepatocellular carcinoma; hsa_circ_0000092; microRNA-338-3p
资金
- Guangxi Science and Technology Project [AD17129025]
Circular RNAs (circRNAs) have been identified in diverse cancers for their role in regulating multiple cellular processes by antagonizing microRNAs (miRNAs or miRs). However, the role of circRNA hsa_circ_0000092 in hepatocellular carcinoma (HCC) still remains enigmatic. Therefore, we aimed to investigate the specific mechanism of hsa_circ_0000092 in HCC. Differentially expressed circRNAs associated to HCC were initially analysed. The expression of hsa_circ_0000092, miR-338-3p and HN1 in HCC tissues and cell lines was examined. Next, the interaction among hsa_circ_0000092, miR-338-3p and HN1 was determined by dual-luciferase reporter, RNA pull-down and northern blot assays. Subsequently, a series of mimic, inhibitor or siRNA plasmids were delivered into HCC cells to validate the effects of hsa_circ_0000092, miR-338-3p and HN1 in controlling cell proliferation, migration, invasion and angiogenesis in vitro. Furthermore, the role of hsa_circ_0000092 in tumour growth of HCC in vivo was assessed with hsa_circ_0000092 depleted with siRNA. The hsa_circ_0000092/miR-338-3p/HN1 axis was predicted to participate in the development of HCC. hsa_circ_0000092 and HN1 were highly expressed while miR-338-3p was poorly expressed in HCC tissues and cell lines. hsa_circ_0000092 could competitively bind to miR-338-3p to up-regulate HN1 expression. Moreover, depleted hsa_circ_0000092 or elevated miR-338-3p was shown to suppress HCC cell proliferation, migration, invasion and angiogenesis in vitro via down-regulation of HN1. Furthermore, silencing hsa_circ_0000092 was demonstrated to suppress tumour growth in HCC in vivo. The results of this study suggested that hsa_circ_0000092 impaired miR-338-3p-mediated HN1 inhibition to aggravate the development of HCC, indicating that hsa_circ_0000092 is a potential candidate marker and therapeutic target for HCC.
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