title: MiR-218 impedes IL-6-induced prostate cancer cell proliferation and invasion via suppression of LGR4 expression.
abstract: 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.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Fujun
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Chaohui
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Fengyan
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Zhankui
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Zhenglei
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Jinjian
authors.initials: J
authors.lastname: Yang
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D020413:3' Untranslated Regions; C508600:IL6 protein, human; D015850:Interleukin-6; C411562:LGR4 protein, human; C547471:MIRN218 microRNA, human; D035683:MicroRNAs; D043562:Receptors, G-Protein-Coupled