Long non-coding RNA (LncRNA) CASC9/microRNA(miR)-590–3p/sine oculis homeobox 1 (SIX1)/NF-κB axis promotes proliferation and migration in breast cancer

Abstract

ABSTRACT Long non-coding RNA (lncRNA)–microRNA–mRNA signaling axes have recently been shown to have a key role in the development of breast cancer (BC). In this study, we investigated how the cancer susceptibility candidate 9 (CASC9) gene affects the cell growth, invasion, migration, and apoptosis of BC cells. The levels of microRNA-590-3p (miR-590-3p), CASC9, and the sine oculis homeobox 1 (SIX1) gene were determined through qRT-PCR. We conducted cell counting kit-8 (CCK-8) assays to assess cell proliferation, transwell assays to detect cell migration/invasion, and flow cytometry to evaluate cell apoptosis. StarBase v2.0 was used to predict interactions between miR-590-3p and SIX1 or CASC9, and dual-luciferase reporter assays were used to verify these predictions. CASC9 protein was overexpressed in BC cells and tissues, while CASC9 knockdown inhibited BC cell growth, invasion, and migration and promoted apoptosis. Additionally, we verified that CASC9 competes for binding with miR-590-3p. Moreover, SIX1 was determined to be a target of miR-590–3p, and SIX1 expression was inhibited by miR-590-3p overexpression. CASC9 enhanced BC development by downregulating miR-590-3p and upregulating SIX1 during the activation of the NF-κB pathway. These data suggest that the CASC9/miR-590-3p/SIX1/NF-κB axis is involved in breast cancer progression, providing insight into the function of CASC9 in breast cancer development.