Hsa_circ_0005986 inhibits carcinogenesis by acting as a miR-129-5p sponge and is used as a novel biomarker for hepatocellular carcinoma

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.

Circular RNA hsa_circ_0000567 can be used as a promising diagnostic biomarker for human colorectal cancer

“…To date, several circRNAs have emerged as new biomarkers in cancers. For example, hsa_circ_0000190 could serve as a biomarker for gastric cancer diagnosis, hsa_circ_0005986 was used as a biomarker in the diagnosis of HCC, and circular RNA ciRS‐7 was identified as a prognostic biomarker in colorectal cancer . In this study, we investigated that hsa_circ_0000567 was downregulated in CRC tissues and CRC cell lines (Figure ).…”

Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2

“…Furthermore, Fu et al . found both hsa_circ_0005986 and hsa_circ_0004018 were downregulated in HCC tissues and cells . Han et al .…”

“…indicated that the upregulation of circ‐ITCH inhibited the in vitro growth and in vivo tumorigenesis of esophageal squamous cell carcinoma cells . Knockdown of hsa_circ_0005986 accelerated the proliferation and the cell cycle of HCC cells . Circ‐MTO1 suppressed HCC tumor growth by targeting miR‐9 and upregulating P21 .…”

“…Fu et al . revealed that hsa_circ_0005986 directly interacted with miR129‐5p, thereby regulating the mRNA expression level of Notch1 . Fu et al .…”

“…Cdr1 antisense locus (CDR1as) plays an oncogenic role in HCC by targeting miR‐7 . Hsa_circ_0005986, as a miR‐129‐5p sponge, inhibits carcinogenesis in HCC . These findings indicate that investigation of the relationship between circRNAs and miRNAs in HCC may be meaningful.…”