Inhibitory effect of the Notch pathway-inhibitor DAPT on invasion and metastasis of tongue cancer via lncRNA-KAT14 regulation

Eur Rev Med Pharmacol Sci. 2020 Jan;24(1):189-199. doi: 10.26355/eurrev_202001_19911.

Abstract

Objective: We aimed to identify a reliable biomarker for tongue squamous cell carcinoma (TSCC), the most common oral cancer with no established biomarkers, to predict prognosis and to select the optimal treatment.

Materials and methods: To investigate whether DAPT exhibited antitumor functions, CAL-27 and SCC-9 cells were treated with DAPT (5 µM or 10 µM) for different times. Further, qRT-PCR was used to determine the mRNA expression levels of lncRNA-KAT14 after treatment with DAPT or si-KAT14 and both combined. Moreover, the treated cells were cultured for different times to investigate their antitumor function. The Wound-healing and Transwell assay were carried out to evaluate the migration and invasion viability of cancer cells, respectively. Finally, the Western blots were performed to determine the expression of EMT-related proteins after transfection with si-KAT14 or treatment with DAPT to investigate the effects of DAPT on EMT-related proteins.

Results: Proliferation was inhibited after treatment with DAPT, and the expression of lncRNA-KAT14 was upregulated. To investigate the correlation of DAPT and lncRNA-KAT14 on the metastasis and invasion in tongue cancer, the following cellular processes were assessed: proliferation, invasion, and migration ability. The Western blots were used to determine the expression of E-cadherin, N-cadherin, Vimentin, and Snail, showing that DAPT or lncRNA-KAT14 suppressed all these processes, inducing a decreased expression of N-cadherin, Vimentin, and Snail, and increased expression of E-cadherin, compared with the control group. Once transfection with si-KAT14 occurred, the evaluated cellular processes were enhanced, being this attenuated by the treatment with DAPT.

Conclusions: Our results suggest that DAPT suppresses invasion and metastasis of tongue cancer by regulating lncRNA-KAT14.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dipeptides / chemistry
  • Dipeptides / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Receptors, Notch / antagonists & inhibitors*
  • Receptors, Notch / metabolism
  • Structure-Activity Relationship
  • Tongue Neoplasms / drug therapy*
  • Tongue Neoplasms / metabolism
  • Tongue Neoplasms / pathology
  • Tumor Cells, Cultured

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • Dipeptides
  • KAT14 protein, human
  • RNA, Long Noncoding
  • Receptors, Notch