MiR-34a functions as a tumor suppressor in oral cancer through the inhibition of the Axl/Akt/GSK-3β pathway

  • J Dent Sci. 2024 Jan;19(1):428-437. doi: 10.1016/j.jds.2023.08.013.
Yu-Fu Su  1  2 ,  Chun-Shu Lin  2 ,  Po-Chien Shen  2 ,  Shuang-En Chuang  3 ,  Yang-Hong Dai  2 ,  Tsai-Wang Huang  4 ,  Che-Yi Lin  5 ,  Yi-Jen Hung  6 ,  Yi-Shing Shieh  7  8  9
Affiliations
  • 1. Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
  • 2. Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
  • 3. National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.
  • 4. Division of Thoracic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
  • 5. Department of Oral and Maxillofacial Surgery, Chi Mei Medical Center, Tainan, Taiwan.
  • 6. Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
  • 7. Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
  • 8. Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
  • 9. School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
PMID: 38303867 DOI: 10.1016/j.jds.2023.08.013
Abstract

Background/purpose: Oral Cancer is a prevalent malignancy affecting men globally. This study aimed to investigate the regulatory role of miR-34a in oral Cancer cells through the Axl/Akt/glycogen synthase kinase-3β (GSK-3β) pathway and its impact on cellular malignancy.

Materials and methods: We examined the effects of miR-34a overexpression on the malignancy of oral Cancer cells. Multiple oral Cancer cell lines were assessed to determine the correlation between endogenous miR-34a and Axl levels. Transfection experiments with miR-34a were conducted to analyze its influence on Axl mRNA and protein expression. Luciferase reporter assays were performed to investigate miR-34a's modulation of Axl gene transcription. Manipulation of miR-34a expression was utilized to demonstrate its regulatory effects on oral Cancer cells through the Axl/Akt/GSK-3β pathway.

Results: Overexpression of miR-34a significantly suppressed the malignancy of oral Cancer cells. We observed an inverse correlation between endogenous miR-34a and Axl levels across multiple oral Cancer cell lines. Transfection of miR-34a resulted in decreased Axl mRNA and protein expression, and luciferase reporter assays confirmed miR-34a-mediated modulation of Axl gene transcription. The study revealed regulatory effects of miR-34a on oral Cancer cells through the Axl/Akt/GSK-3β pathway, leading to alterations in downstream target genes involved in cellular proliferation and tumorigenesis.

Conclusion: Our findings highlight the significance of the miR-34a/Axl/Akt/GSK-3β signaling axis in modulating the malignancy of oral Cancer cells. Targeting miR-34a may hold therapeutic potential in oral Cancer treatment, as manipulating its expression can attenuate the aggressive behavior of oral Cancer cells via the Axl/Akt/GSK-3β pathway.

Keywords
Axl; MiR-34a; Oral cancer; Targeted therapy.
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