Abstract
BackgroudAccumulating evidences indicate that circular RNAs (circRNAs), a class of non-coding RNAs, play important roles in tumorigenesis. However, the function of circRNAs in hepatocellular cancer (HCC) is largely unknown.MethodsWe performed circRNA microarrays to identify circRNAs that are aberrantly expressed in HCC tissues. Expression levels of a significantly upregulated circRNA, circFBLIM1, was detected by quantitative real-time PCR (qRT-PCR) in HCC cell lines and tissues. Then, we examined the functions of circFBLIM1 in HCC by cell proliferation, apoptosis, invasion and mouse xenograft assay. In addition, luciferase assay and RNA immunoprecipitation (RIP) assay were used to explore the miRNA sponge function of circFBLIM1 in HCC.ResultsMicroarray analysis and qRT-PCR verified a circRNA termed circFBLIM1 that was upregulated in HCC tissues and cell lines. Knockdown of circFBLIM1 inhibited proliferation, invasion and promoted apoptosis in HCC. Via luciferase reporter assays, circFBLIM1 and FBLIM1 were observed to directly bind to miR-346. Subsequent experiments showed that circFBLIM1 and FBLIM1 regulated the expression of each other by sponging miR-346.ConclusionsTaken together, we conclude that circFBLIM1 may function as a competing endogenous RNA (ceRNA) to regulate FBLIM1 expression through sponging miR-346 to exert regulatory functions in HCC. circFBLIM1 may be a diagnostic biomarker and potential target for HCC therapy.
Highlights
Liver cancer is a common malignant disease
We found 6024 circRNAs downregulated with fold change greater than 2, P < 0.05 in hepatocellular cancer (HCC) tissue, while 10,720 circRNAs upregulated by the same cutoff
The variation of circRNAs expression was revealed in the scatter plot (Fig. 1b). quantitative real-time PCR (qRT-PCR) was performed to verify the expression of the top five upregulated circRNAs in three HCC cell lines (Fig. 1c-g)
Summary
Liver cancer is a common malignant disease. It is estimated that there were 782,500 new cases and 745,500 deaths of liver cancer during 2012 worldwide [1]. Most primary liver cancer cases are hepatocellular cancer (HCC), which tends to be diagnosed at advanced stage, and the curative treatments are surgical resection or transplantation. Despite the improvement of surgical technique and radio-chemotherapy regimens in the past decades, the prognosis of HCC remains poor [2,3,4]. It has been reported that many genes relate to the carcinogenesis of HCC, the molecular mechanisms remain mostly obscure [5]. It urges us to search novel molecular targets to develop more effective therapeutic strategies for HCC
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