Abstract
Circular RNAs (circRNAs), a class of long-time-ignored noncoding RNA, have been revealed as multifunctional RNAs in recent years. However, the diagnostic values and the mechanism of most circRNAs in hepatocellular carcinoma (HCC) remain unknown. In this study, we revealed that the expression level of hsa_circ_0005986 in HCC was significantly lower than that in adjacent non-tumorous tissues (P < 0.001). Its levels in HCC cell lines, HepG2, SMMC7721, Huh7, MHCC97L, MHCC97H, and HCCLM3 were significantly lower than those in human normal hepatic cell line L02 (P < 0.001). In addition, the low expression level of hsa_circ_0005986 was correlated with chronic hepatitis B family history (P = 0.001), tumor diameters (P < 0.001), microvascular invasion (P = 0.026), and Barcelona Clinic Liver Cancer (BCLC) stage (P < 0.001). Further experiments demonstrated that both hsa_circ_0005986 and Notch1mRNA were targets of miR-129-5p, and that hsa_circ_0005986 downregulation liberated miR-129-5p and decreased the expression level of Notch1mRNA. More importantly, hsa_circ_0005986 downregulation accelerated cell proliferation by promoting the G0/G1 to S phase transition. We conclude that hsa_circ_0005986 function as microRNA sponge in tumorigenesis and can be used as a novel biomarker for HCC.
Highlights
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer [1, 2]
The carcinogenesis of hepatocellular carcinoma (HCC) has been recognized as a complex process over many years; and its clinical diagnosis often happens at an advanced stage, generally missing the best time for radical treatments
The early diagnosis is imperative for prognosis of HCC [23]
Summary
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer [1, 2]. Researchers have reported that circRNAs are involved in carcinogenesis of several types of cancers, such as gastric cancer, colorectal cancer, ovarian cancer and HCC [6, 9,10,11,12]. Harboring miRNA response elements (MREs), some circRNAs act as competing endogenous RNAs (ceRNAs) to play their biological roles, especially in cancer. CircHIPK3 regulates cell growth by sponging multiple miRNAs [13]; circITCH plays an inhibitory role in esophageal squamous cell carcinoma (ESCC) by suppressing the Wnt/β-catenin pathway through interacting with multiple miRNAs [14]; Cdr antisense locus (CDR1as) acts as an oncogene partly through targeting miR-7 in HCC [15]. The function of most circRNAs in HCC and their clinical significance remain unknown
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