CAPN6 Regulates Uterine Leiomyoma Cell Proliferation and Apoptosis through the Rac1-Dependent Signaling Pathway.

OBJECTIVE:Calpain 6 (CAPN6) is one of the calcium-dependent intracellular nonlysosomal proteases that are dysregulated in uterine leiomyomas (UtLMs). However, its function and mechanism in UtLMs is still unknown. METHODS:The correlation between CAPN6 expression and UtLMs was analyzed by the Gene Expression Omnibus (GEO). The expression of CAPN6 and Rac1 was detected by quantitative real-time PCR (qPCR) and western blot analysis. Cell proliferation ability was analyzed by a Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was detected by flow cytometry. RESULTS:CAPN6 was overexpressed in UtLMs compared with uterine smooth muscle cells (UtSMCs). The downregulation of CAPN6 resulted in decreased cell proliferation and increased apoptosis of UtLMs. Furthermore, mechanical investigations revealed that these inhibitory effects were correlated with Rac1/PAK1 signaling pathways. Silencing the expression of CAPN6 resulted in decreased Rac1 and phospho-PAK1. On the other hand, upregulated Rac1 expression could reverse the reduced phosphorylation of PAK1 induced by CAPN6 silencing. CONCLUSIONS:This data suggests that CAPN6 regulates UtLMs proliferation and apoptosis while being mediated through the Rac1/PAK1 signaling pathway.

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