RECQL1 plays an important role in the development of tongue squamous cell carcinoma

Cell Physiol Biochem. 2014;33(5):1579-90. doi: 10.1159/000358721. Epub 2014 May 16.

Abstract

Background/aims: RECQL1, a member of the human RECQ helicase family, participates in DNA repair. Recent reports showed that RECQL1 silencing in cancer cells resulted in mitotic catastrophe, which prevented tumor growth in murine models. However, its therapeutic potential has never been examined in tongue squamous cell carcinoma (SCC).

Methods: To explore the role of RECQL1 in the development of tongue SCC, we used RNA interference technology to silence RECQL1 in SCC-9 and SCC-15 human tongue SCC cell lines, and to subsequently evaluate its effects both in vitro and in vivo.

Results: After RECQL1 was silenced in SCC cells by siRNA, we observed downregulation of RECQL1 mRNA and protein in cancer cells. RECQL1 is one of the predicted miR-203 targets, and we found that miR-203 downregulated the expression of RECQL1 at the post-transcriptional level. RECQL1-shRNA or miR-203 overexpression inhibited SCC-9 cell growth. In addition, there was accumulation of cells in the sub-G1 fraction and increased apoptosis 72 h post-transfection. In addition, knockdown of RECQL1 led to a strong anticancer effect, as the tumorigenicity of SCC-9 cells was inhibited in vivo. Moreover, we found that two immunosuppressive factors were also significantly downregulated upon RECQL1 knockdown or miR-203 overexpression in vitro.

Conclusion: Collectively, these results indicate that RECQL1 plays an important regulatory role in cancer cell proliferation and tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Down-Regulation / drug effects
  • Drug Screening Assays, Antitumor
  • Gene Silencing / drug effects
  • Humans
  • Immunosuppressive Agents / pharmacology
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • RecQ Helicases / antagonists & inhibitors
  • RecQ Helicases / genetics
  • RecQ Helicases / metabolism*
  • Structure-Activity Relationship
  • Tongue Neoplasms / drug therapy
  • Tongue Neoplasms / metabolism*
  • Tongue Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Immunosuppressive Agents
  • MIRN203 microRNA, human
  • MicroRNAs
  • RecQ Helicases