Prostate cancer is the most common solid-organ
malignancy and the second leading cause of
cancer-related death in males. The oncogenic effect of
leucine-rich repeat-containing
G protein-coupled receptor (LGR) 4 has been recognized in the formation of various types of
cancers, yet its regulatory mechanism in
prostate cancer is still not fully understood. Previous study has shown that LGR4 may be a new responsive gene of
interleukin-6 (IL-6) in
cancer progression. In the present study, we established the LNCaP-IL-6+ cell subline by long-term incubation with a low concentration of
IL-6 and explored the regulatory role of miR-218, a
tumor-suppressing
miRNA, in IL-6-induced LGR4 expression and LNCaP-IL-6+ cell proliferation and invasion. The results showed that miR-218 expression was gradually decreased and
IL-6 expression was gradually increased in the process of
prostate cancer progression from normal prostate,
benign prostatic hyperplasia to
prostate cancer, and from LNCaP to LNCaP-IL-6+ cells. Notably, we also found that miR-218 inhibited the expression of cell cycle regulatory
protein cyclin A1 and invasion-related
matrix metalloproteinase-9 protein induced by
IL-6, and impeded the accelerative effect of
IL-6 on LNCaP-IL-6+ cell proliferation, cell cycle progression and cell invasion. Moreover, our results confirmed that miR-218 directly targets LGR4 and modulated the PI3K/Akt and Wnt/β-
catenin pathways in the LNCaP-IL-6+ cells. Taken together, these data clearly demonstrated the involvement of the miR-218/LGR4 regulatory pathway in IL-6-induced cell proliferation and invasion in LNCaP-IL-6+ cells via PI3K/Akt and Wnt/β-
catenin signaling, providing new insight into
therapeutics for
inflammation-induced
prostate cancer.