MicroRNA-590-3p promotes cell proliferation and invasion by targeting inositol polyphosphate 4-phosphatase type II in human prostate cancer cells.

Abstract

Inositol polyphosphate 4-phosphatase type II emerges as a tumor suppressor in prostate cancer, and its loss of expression is associated with poor prognosis for prostate cancer. However, the mechanism of downregulation of inositol polyphosphate 4-phosphatase type II in prostate cancer development has not yet been fully clarified. In this study, microRNA-590-3p was found to be upregulated in both prostate cancer tissues and cell lines. Overexpression of microRNA-590-3p by microRNA-590-3p mimics promoted prostate cancer cell proliferation and invasion and accelerated the growth of xenografted tumors, while microRNA-590-3p inhibitors contributed to inhibition of cellular proliferation and invasion as well as tumor growth. A dual-luciferase reporter assay and expression analysis further confirmed that inositol polyphosphate 4-phosphatase type II was a direct target of microRNA-590-3p. Enforced expression of microRNA-590-3p led to repression of inositol polyphosphate 4-phosphatase type II messenger RNA and protein expression, as well as upregulation of p-Akt, p-FoxO3a, and cyclin D1 and downregulation of p21 expression in prostate cancer cell lines. Overexpression of inositol polyphosphate 4-phosphatase type II could reduce microRNA-590-3p-induced cell proliferation and invasion as well as tumor growth, and decrease microRNA-590-3p-mediated upregulation of cyclin D1 and downregulation of p21 expression in prostate cancer cells. Taken together, our findings reveal that microRNA-590-3p is a potential onco-microRNA that participates in carcinogenesis of human prostate cancer by suppressing inositol polyphosphate 4-phosphatase type II expression and involving the Akt/FoxO3a pathway. MicroRNA-590-3p may represent a potential therapeutic target for prostate cancer patients.

• Authors: Haiwen Chen, Qidong Luo, Hongliang Li
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 39 Issue 3 Pg. 1010428317695941 (Mar 2017) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 28345464 (Publication Type: Journal Article)

Chemical References

• CCND1 protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• FOXO3 protein, human
• Forkhead Box Protein O3
• MIRN590 microRNA, human
• MicroRNAs
• RNA, Messenger
• Cyclin D1
• Proto-Oncogene Proteins c-akt
• Phosphoric Monoester Hydrolases
• phosphatidylinositol-3,4-bisphosphate 4-phosphatase

Topics

• Animals
• Carcinogenesis (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Cyclin D1 (metabolism)
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• Female
• Forkhead Box Protein O3 (metabolism)
• Gene Expression Regulation, Neoplastic
• Genes, Tumor Suppressor
• HEK293 Cells
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics)
• Neoplasm Invasiveness (genetics)
• Neoplasm Transplantation
• Phosphoric Monoester Hydrolases (metabolism)
• Prognosis
• Prostatic Neoplasms (genetics, mortality, pathology)
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Messenger (genetics)
• Transplantation, Heterologous