Piwi-interacting RNA-651 promotes cell proliferation and migration and inhibits apoptosis in breast cancer by facilitating DNMT1-mediated PTEN promoter methylation

Abstract

ABSTRACT Piwi-interacting RNAs (piRNAs/piRs) are small non-coding RNAs that play important roles in stablizing genome through silencing transposable genetic elements. The piR-651 was reported to be dysregulated in several human solid cancer tissues, such as gastric and lung cancers. However, the role of piRNA-651 in carcinogenesis of breast cancer has not been defined. We found that piR-651 was highly expressed in breast cancer tissues and cell lines. Overexpression of piR-651 facilitated cell proliferation and invasion, restrained cell apoptosis and the percentage of arrested cells in G0/G1 phase, accompanied by upregulated expression of oncogenes (MDM2, CDK4 and Cyclin D1), whereas piR-651 downregulation showed the opposite effects. Additionally, piR-651 could promote phosphatase and tensin homolog (PTEN) methylation and its downregulated expression by recruiting DNA methyltransferase 1 (DNMT1) to the PTEN promoter region through complex formation with PIWIL2. PTEN overexpression reversed the effects of upregulated piR-651 on cell functions. This study reveals that piR-651 promotes proliferation and migration and induces apoptosis of breast cancer cells by facilitating DNMT1-mediated PTEN promoter methylation, which may provide a potential therapeutic mechanism for breast cancer.