MiR-34a functions as a tumor suppressor in oral cancer through the inhibition of the Axl/Akt/GSK-3β pathway
Yu–Fu Su, Chun‐Shu Lin, Po‐Chien Shen, Shuang‐En Chuang, Yang-Hong Dai, Tsai-Wang Huang, Che-Yi Lin, Yi‐Jen Hung, Yi‐Shing Shieh
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.