Hsa-circ-0000098 promotes the progression of hepatocellular carcinoma by regulation of miR-136-5p/MMP2 axis.

Abstract

Many papers revealed the abnormal expression of circular RNA (circRNA), a kind of non-coding RNA, in mammals. However, the potential functional mechanisms are still unknown. In this paper, we aimed to elucidate the function and mechanisms of hsa-circ-0000098 in hepatocellular carcinoma (HCC). Bioinformatics was used to analyze the Gene Expression Omnibus (GEO) database (GSE97332) and predict the targeted gene site of miR-136-5p. The starBase online database was utilized to predict that MMP2 is the downstream target gene of miR-136-5p. The expression of hsa_circ_0000098, miR-136-5p and matrix metalloproteinase 2 (MMP2) in HCC tissues or cells was detected using quantitative real-time polymerase chain reaction (qRT-PCR) method. The migration and invasion abilities of processing cells were measured with transwell assay. The luciferase reporter assay was carried out to verify the targets of hsa_circ_0000098, MMP2 and miR-136-5p. The western blot assay was performed to detect the expression of MMP2, MMP9, E-cadherin, and N-cadherin. According to the analysis of GEO database of GSE97332, hsa_circ_0000098 had a prominent expression in HCC tissues. A continued analysis of relevant patients has verified that the high expression of hsa_circ_0000098 is present in HCC tissues with relative to poor prognosis. We also proved that the migration and invasion abilities of HCC cell lines can be inhibited by silencing hsa_circ_0000098. In view of the above findings, we continued to study the hsa_circ_0000098 mechanism of action in HCC. The study revealed that hsa_circ_0000098 can sponge miR-136-5p and then regulate MMP2, which is a downstream target gene of miR-136-5p, in order to promote HCC metastasis by regulation of miR-136-5p/MMP2 axis. Our data showed that has_circ_0000098 facilitates the migration, invasion and malignant progression of HCC. On the other hand, we demonstrated that the mechanism of action of hsa_circ_0000098 in HCC might be due to the regulation of miR-136-5p/MMP2 axis.