Circular RNA circ_0001955 promotes hepatocellular carcinoma tumorigenesis by up-regulating alkaline ceramidase 3 expression through microRNA-655-3p

Bioengineered. 2022 Feb;13(2):2099-2113. doi: 10.1080/21655979.2021.2023797.

Abstract

The involvement of certain circular RNAs (circRNAs) in the development of hepatocellular carcinoma (HCC) has been reported. Herein, this study aimed to investigate the function and mechanism of circ_0001955 in HCC tumorigenesis. Expression of circ_0001955, miR-655-3p, and alkaline ceramidase 3 (ACER3) was evaluated by quantitative real-time PCR and Western blot. Cell counting kit-8, colony formation, transwell, tube formation, flow cytometry and tumor xenograft assays were adopted to perform in vitro and in vivo experiments. The direct interaction between miR-655-3p and circ_0001955 or ACER3 was verified using dual-luciferase reporter and RNA immunoprecipitation assays. Circ_0001955 was highly expression in HCC tissues and cells. Functionally, circ_0001955 deletion suppressed HCC tumorigenesis in vitro by suppressing cell growth, metastasis and angiogenesis. Mechanistically, circ_0001955 could competitively sponge miR-655-3p, which targeted ACER3. Besides that, miR-655-3p silencing abolished the anticancer action of circ_0001955 silencing on HCC cells. Moreover, miR-655-3p overexpression inhibited HCC cell oncogenic phenotypes mentioned above, which were attenuated by ACER3 up-regulation. Additionally, circ_0001955 knockdown also impeded HCC growth in a mouse model. In all, this study suggested a novel circ_0001955/miR-655-3p/ACER3 pathway in HCC progression.

Keywords: ACER3; circ_0001955; hepatocellular carcinoma; miR-655-3p; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Alkaline Ceramidase / biosynthesis*
  • Alkaline Ceramidase / genetics
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • RNA, Circular
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Up-Regulation*

Substances

  • MIRN655 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Circular
  • RNA, Neoplasm
  • ACER3 protein, human
  • Alkaline Ceramidase

Grants and funding

This study was supported by Joint Co-construction Project of Henan Medical Science and Technology Research Plan (No.LHGJ20190138).