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

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

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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