Hsa_circ_0081069 facilitates tongue squamous cell carcinoma progression by modulating MAP2K4 expression via miR-634

Odontology. 2023 Apr;111(2):474-486. doi: 10.1007/s10266-022-00746-0. Epub 2022 Oct 1.

Abstract

It has been demonstrated that circular RNA (circRNA) is involved in the progression of tongue squamous cell carcinoma (TSCC). The aim of this study was to investigate the intrinsic mechanism of circ_0081069 in TSCC progression. The expression levels of circ_00081069, miR-634, and mitogen-activated protein kinase kinase 4 (MAP2K4) in TSCC tissues and cells were detected by quantitative real-time PCR (qRT-PCR). Cell counting kit 8 assay, Edu assay, and flow cytometry assay were used to detect cell proliferation and cell cycle distribution. Transwell assay was used to detect cell migration and invasion abilities. Western blot analysis was performed to detect the protein expression. Dual-luciferase reporter assay was used to detect the targeting relationships of circ_0081069, miR-634 and MAP2K4. Immunohistochemical staining was used to measure MAP2K4-positive cells in tissues. The effect of circ_0081069 silencing on tumor formation in TSCC in vivo was explored by xenograft tumor assay. Circ_0081069 was highly expressed in TSCC tissues and cells. Silencing of circ_0081069 inhibited cell proliferation, cell cycle progress, cell migration and invasion in vitro, as well as hindered tumor growth in vivo. Mechanistically, circ_0081069 targeted miR-634 to negatively regulate miR-634 expression, and inhibition of miR-634 was able to weaken the inhibitory effect of circ_0081069 knockdown on proliferation, migration, and invasion of TSCC cells. MiR-634 targeted MAP2K4 and negatively regulated MAP2K4 expression, and overexpression of miR-634 inhibited TSCC cell proliferation, migration, and invasion, while co-overexpression of MAP2K4 was able to reverse the effects of miR-634 in TSCC cells. Circ_0081069 is involved in the regulation of proliferation, cycle progress, migration, and invasion of TSCC cells through the miR-634/MAP2K4 axis and has the potential to serve as a diagnostic biomarker and therapeutic target.

Keywords: MAP2K4; Tongue squamous cell carcinoma; circ_0081069; miR-634.

MeSH terms

  • Carcinoma, Squamous Cell* / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Humans
  • MAP Kinase Kinase 4
  • MicroRNAs* / genetics
  • Tongue
  • Tongue Neoplasms* / genetics

Substances

  • MicroRNAs
  • MAP2K4 protein, human
  • MAP Kinase Kinase 4
  • MIRN-634 microRNA, human