Abstract
Increasing evidence shows that circular RNAs (circRNAs) play a regulatory role in cancer. In the present study, we aimed to investigate the characteristics and effects of hsa_circ_0026134 in hepatocellular carcinoma (HCC). We investigated hsa_circ_0026134 expression in 20 pairs of clinical tissues from HCC patients; expression of hsa_circ_0026134 in different cell lines; effect of hsa_circ_0026134 on proliferation and invasion of HCC cell lines; and the regulatory mechanisms and interactions among hsa_circ_0026134, miR-127-5p, tripartite motif-containing protein 25 (TRIM25) and insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3). hsa_circ_0026134 expression was increased in HCC samples and cell lines. Down-regulation of hsa_circ_0026134 attenuated HCC cell proliferation and metastatic properties. Micro (mi)RNA (miR)-127-5p was sponged by hsa_circ_0026134. Rescue experiments indicated that inhibition of miR-127-5p expression promoted cell proliferation and invasion even after hsa_circ_0026134 silencing. TRIM25 and IGF2BP3 were targets of miR-127-5p. Overexpression of TRIM25 or IGF2BP3 promoted cell proliferation and invasion in cells overexpressing miR-127-5p. Down-regulation of hsa_circ_0026134 suppressed TRIM25- and IGF2BP3-mediated HCC cell proliferation and invasion via promotion of miR-127-5p expression, which have been confirmed by luciferase reporter assay. The present study provides a new treatment target for HCC.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy and is a serious health problem worldwide [1,2]
Increasing evidence shows that noncoding RNA plays an important role in regulation of tumorigenesis. ncRNA including miRNA, long ncRNA and circular RNA [4,5,6]. miRNA and lncRNA have been extensively studied in various tumors, such as glioblastoma [7], gastric cancer [8], liver cancer [9], colorectal cancer [10] and bladder cancer [11]
Hsa circ 0026134 was named circular RNA (circRNA) TUBA1C (Figure 1A). quantitative reverse transcription-polymerase chain reaction (qRT-PCR) detection showed that expression of hsa circ 0026134 in HCC samples was significantly increased when compared with their normal counterparts (Figure 1B). qRT-PCR uncovered that hsa circ 0026134 level was markedly enhanced in HepG2, HepaRG, LM3 and SK-Hep1 cells relative to the human normal epithelium cell line (LO-2) (Figure 1C)
Summary
Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy and is a serious health problem worldwide [1,2]. MiRNA and lncRNA have been extensively studied in various tumors, such as glioblastoma [7], gastric cancer [8], liver cancer [9], colorectal cancer [10] and bladder cancer [11]. Their role in oncogenesis and development of circRNA is still largely unclear
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