Long non coding RNA OIP5‑AS1 promotes metastasis of breast cancer via miR‑340‑5p/ZEB2 axis.

Abstract

Breast cancer is the most common invasive cancer in women with the highest number of related deaths which is caused by distal metastasis. Recently, integrated analysis of gene expression profile suggested widespread gene dysregulation in various types of cancer. Research in the past decade has focused on long non-coding RNAs (lncRNAs), particularly in cell proliferation, tumor progression and metastasis. OPA-interacting protein 5 antisense transcript 1 (OIP5-AS1) is an evolutionarily conserved long non-coding RNA that has been linked to oncogenesis in multiple cancers. In breast cancer, dysregulation of OIP5-AS1 was reported but the precise role in cancer development and progression remains unclear. In the present study, using small interfering RNA (siRNA) targeting OIP5-AS1, it was shown that knockdown of OIP5-AS1 was associated with alteration of EMT markers and suppressed migration and invasion of breast cancer cells. Among the EMT-related transcription factors, ZEB1 and ZEB2 were significantly downregulated with OIP5-AS1 knockdown. Computational analysis and a dual-luciferase reporter system identified miR-340-5p was the target gene for OIP5-AS1. Further experiments verified the function of OIP5-AS1 in cell invasion was dependent on miR-340a-5p through regulating target gene ZEB2. In vivo study demonstrated that overexpressing OIP5-AS1 in breast cancer cells promoted lung metastasis in nude mice. The findings of the present study revealed the mechanism of OIP5-AS1 in breast cancer metastasis. Overall, our study may provide a potential therapeutic target for breast cancer metastasis.