TITLE:
miR-221/222/PUMA Axis Promotes Oral Squamous Cell Carcinoma Apoptosis
AUTHORS:
Fangfang Jiang, Qiaoyun Huang, Jiexiang Nian, Shenghui Yang
KEYWORDS:
miR-221/222, Apoptosis, Oral Squamous Cell Carcinoma, PUMA, Target
JOURNAL NAME:
Open Journal of Stomatology,
Vol.13 No.10,
October
30,
2023
ABSTRACT: Background: To investigate the therapeutic activity of the miR-221/222 inhibitor against OSCC in vitro and in vivo. Materials and Methods: HSC3 and HSC6 were treated with miR-221/222 inhibitor and the empty vector respectively. After the recombinants were transfected into HSC3 and HSC6 with LipofectamineTM MAX, the expression of miR-221/222 and PUMA was analyzed by RT-PCR. The proliferation and migration of HSC3 and HSC6 were detected by CCK-8 assay and Wound-healing assay. Cell cycle and apoptosis were detected by flow cytometry. The effect of the miR-221/222 inhibitor was also assessed in OSCC xenografts in BALB/c-nu mice. Results: Transfection of the miR-221/222 inhibitor increased cell apoptosis and upregulated PUMA expression in OSCC cell lines HSC3 and HSC6 with the significantly reduced expression of miR-221 and miR-222. Furthermore, the miR-221/222 inhibitor suppressed cell growth and invasion and blocked the cell cycle at the G1 phase. Obvious anti-tumor activity was achieved in BALB/c-nu mice by treatment with the miR-221/222 inhibitor, together with the upregulation of PUMA protein in tumors retrieved from the mice. Conclusions: There was a significant inhibitory effect of the miR-221/222 inhibitor on the growth of OSCC both in vitro and in vivo, and there might be a regulatory loop between miR-221/222 and PUMA. These findings demonstrated that downregulation of miR-221/222 could induce cell apoptosis, and it might be considered as a candidate target for gene therapy of OSCC.