CircRNA hsa_circ_0070934 functions as a competitive endogenous RNA to regulate HOXB7 expression by sponging miR‑1236‑3p in cutaneous squamous cell carcinoma

Int J Oncol. 2020 Aug;57(2):478-487. doi: 10.3892/ijo.2020.5066. Epub 2020 May 14.

Abstract

Circular ribonucleic acids (circRNAs) serve a vital role in the pathological processes of a number of diseases. Previous microarray results of circRNA expression revealed that hsa_circ_0070933 and hsa_circ_0070934, two circRNAs associated with the La ribonucleoprotein 1B gene, were highly expressed in cutaneous squamous cell carcinoma (CSCC). The present study aimed to explore the specific role of these circRNAs in CSCC. Through reverse transcription‑quantitative PCR, hsa_circ_0070933 and hsa_circ_0070934 expression levels in CSCC cell lines and a human keratinocyte cell line were detected. Additionally, direct interactions between miR‑1236‑3p and HOXB7 or circ‑0070934 were identified using RNA binding protein immunoprecipitation assays and dual‑luciferase reporter assays. Cell Counting Kit‑8, 5‑ethynyl‑2'‑deoxyuridine, Transwell invasion and flow cytometry assays were used to assess the roles of miR‑1236‑3p or circ‑0070934 in cell invasion, proliferation and apoptosis. Subsequently, in vivo tumor formation assays were used to verify the role of circ‑0070934 in CSCC. The results demonstrated that the expression of circ‑0070934 was stably upregulated in a number of CSCC cell lines compared with that in normal human keratinocytes. Knockdown of circ‑0070934 inhibited the invasive and proliferative potential of CSCC cells and promoted apoptosis both in vivo and in vitro. In addition, circ‑0070934 modulated HOXB7 expression through competitive binding with miR‑1236‑3p. In conclusion, the results of the present study demonstrated the effects of the circ‑0070934/miR‑1236‑3p/HOXB7 regulatory axis on CSCC and provided a novel insight for the pathogenesis of CSCC.

Keywords: cutaneous squamous cell carcinoma; circular ribonucleic acids; competing endogenous RNAs; cell proliferation; cell invasion.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Computational Biology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Homeodomain Proteins / genetics*
  • Humans
  • Keratinocytes
  • Mice
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Skin / pathology
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • HOXB7 protein, human
  • Homeodomain Proteins
  • MIRN1236 microRNA, human
  • MicroRNAs
  • RNA, Circular