MicroRNA-4429 suppresses proliferation of prostate cancer cells by targeting distal-less homeobox 1 and inactivating the Wnt/β-catenin pathway

Abstract

Abstract Background Emerging evidence suggests that microRNAs (miRNAs) play multiple roles in human cancers through regulating mRNAs and distinct pathways. This paper focused on the functions of miR-4429 in prostate cancer (PCa) progression and the molecules involved. Methods Expression of miR-4429 in PCa tissues and cells was determined. Upregulation of miR-4429 was introduced in PCa cells to examine its role in the malignant behaviors of cells. The putative target mRNA of miR-4429 involved in PCa progression was predicted from a bioinformatic system and validated through luciferase assays. Overexpression of distal-less homeobox 1 (DLX1) was further induced in cells to validate its implication in miR-4429-mediated events. The activity of Wnt/β-catenin pathway was determined. Results miR-4429 was poorly expressed in PCa tissues and cells. Artificial upregulation of miR-4429 significantly reduced proliferation, growth, invasion, migration and resistance to death of cancer cells and inactivated the Wnt/β-catenin pathway. DLX1 mRNA was found as a target of miR-4429. Upregulation of DLX1 restored the malignant behaviors of PCa cells which were initially suppressed by miR-4429, and it activated the Wnt/β-catenin pathway. Conclusion Our study highlights that miR-4429 inhibits the growth of PCa cells by down-regulating DLX1 and inactivating the Wnt/β-catenin pathway. This finding may offer novel insights into PCa treatment.

Keywords

• Prostate cancer
• MicroRNA-4429
• Wnt/β-catenin pathway
• DLX1
• Biological behavior