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Mir-27a: A Regulator of Apaf-1, Modulate Proliferation and Apoptosis in Laryngeal Carcinoma

Xu Ji, Xiao-Wen Zhang, Ning Liu, Guang-Bin Qiu, Zhen-Ming Xu and Wei-Neng Fu

Purpose: APAF-1, a key mediator in cytochrome C-dependent apoptotic pathway, plays a critical role in many cancers. MicroRNA-27a inhibits hypoxia-induced neuronal apoptosis by targeting APAF-1. Whether microRNA-27a participates in carcinogenesis via regulating APAF-1 is not reported.

Methods: Laryngeal cancer tissues, Hep2 cell line and HEK293 cell line were used in the study. qRT-PCR was used to detect microRNA-27a and APAF-1 mRNA levels. Western blot was to monitor APAF-1 protein level. Cell viability, colony formation and apoptosis assays were applied to evaluate the function of microRNA-27a and APAF-1 in laryngeal cancer. Dual-luciferase reporter assay was to detect the binding ability of microRNA-27a to APAF-1 3'UTR.

Results: In the study, we found that up-regulation of microRNA-27a was negatively correlated with downregulation of APAF-1 in laryngeal cancer. MicroRNA-27a was reconfirmed to directly bind APAF-1 mRNA 3'UTR. Similar to si-APAF-1, ectopic miR-27a significantly promoted laryngeal cancer cell proliferation and colony formation ability and suppressed early apoptosis compared to the controls.

Conclusion: miR-27a acts as a potentially oncogenic role in laryngeal squamous cell carcinoma partly though repressing APAF-1 expression, which enriches regulatory network of APAF-1 mediating apoptotic pathway.