Apelin Promotes Prostate Cancer Metastasis by Downregulating TIMP2 via Increases in miR-106a-5p Expression

Abstract

Prostate cancer commonly affects the urinary tract of men and metastatic prostate cancer has a very low survival rate. Apelin belongs to the family of adipokines and is associated with cancer development and metastasis. However, the effects of apelin in prostate cancer metastasis is undetermined. Analysis of the database revealed a positive correlation between apelin level with the progression and metastasis of prostate cancer patients. Apelin treatment facilitates cell migration and invasion through inhibiting tissue inhibitor of metalloproteinase 2 (TIMP2) expression. The increasing miR-106a-5p synthesis via c-Src/PI3K/Akt signaling pathway is controlled in apelin-regulated TIMP2 production and cell motility. Importantly, apelin blockade inhibits prostate cancer metastasis in the orthotopic mouse model. Thus, apelin is a promising therapeutic target for curing metastatic prostate cancer.

Evaluation of miR-148a-3p and miR-106a-5p as Biomarkers for Prostate Cancer: Pilot Study

“…Inhibition of apelin has been found to reduce PCa metastasis in an orthotopic mouse model. These findings suggest that apelin could be a novel therapeutic target in metastatic PCa [28]. Dhar et al showed that miR-106a-5p expression is significantly associated with PCa progression and validated a PTEN tumor suppressor as a critical target of this on-comiR in PCa cells with a possibility of being used as a chemopreventive and predictive biomarker in the development of PCa [29].…”