Circular RNA circ_0008934 promotes hepatocellular carcinoma growth and metastasis through modulating miR-1305/TMTC3 axis

Hum Cell. 2022 Mar;35(2):498-510. doi: 10.1007/s13577-021-00657-2. Epub 2022 Jan 11.

Abstract

Circular RNAs (circRNAs) play important roles in the progression of hepatocellular carcinoma (HCC). However, the exact function of circ_0008934 in HCC is unknown. Our study aimed to investigate the expression characteristics of circ_0008934 in HCC and its effects on the proliferation and metastasis of HCC, and to explore the potential mechanism. In this study, circ_0008934 expression was found to be significantly upregulated in HCC tissues and cell lines by qRT-PCR. High level of circ_0008934 is closely associated with higher serum AFP (P < 0.001), larger tumor diameter (P = 0.012), microvascular invasion (P = 0.008) and poorer prognosis (P = 0.007) of HCC patients. Functionally, knockdown of circ_0008934 inhibited HCC cell proliferation, invasion and migration in vitro and vivo. Mechanically, circ_0008934 was a sponge of miR-1305 to facilitate the TMTC3 expression, and the TMTC3 expression in HCC tissues was negatively associated with the survival of HCC patients. Furthermore, rescued assays revealed that the circ_0008934 facilitated HCC proliferation, invasion and migration by regulating miR-1305/ TMTC3 signaling pathways. Overall, these results demonstrate that downregulation of circ_0008934 repress HCC growth and metastasis by upregulating miR-1305 to inhibit TMTC3, suggesting circ_0008934/ miR-1305/ TMTC3 regulatory axis may be a possible novel therapeutic target for HCC.

Keywords: Growth; Hepatocellular carcinoma; Metastasis; TMTC3; circ_0008934; miR-1305.

MeSH terms

  • Carcinoma, Hepatocellular* / pathology
  • Carrier Proteins / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / pathology
  • Membrane Proteins / genetics
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular*
  • Signal Transduction

Substances

  • Carrier Proteins
  • MIRN1305 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • RNA, Circular
  • TMTC3 protein, human