title: MiRNA-296-3p-ICAM-1 axis promotes metastasis of prostate cancer by possible enhancing survival of natural killer cell-resistant circulating tumour cells.
abstract: Natural killer (NK) cells are important in host to eliminate circulating tumour cells (CTCs) in turn preventing the development of tumour cells into metastasis but the mechanisms are very poorly defined. Here we find that the expression level of miR-296-3p is much lower in the non-metastatic human prostate cancer (PCa) cell line P69 than that in the highly metastatic cell line M12, which is derived from P69. We demonstrate that miR-296-3p directly targets and inhibits the expression of intercellular adhesion molecule 1 (ICAM-1) in the malignant M12. The data from clinical tissue microarrays also show that miR-296-3p is frequently upregulated and ICAM-1 is reversely downregulated in PCa. Interestingly, ectopic expression of miR-296-3p in P69 increases the tolerance to NK cells whereas knockdown of miR-296-3p in M12 reduces the resistance to NK cells, which both phenotypes can be rescued by re-expression or silencing of ICAM-1 in P69 and M12, respectively. These results are also manifested in vivo by the decrease in the incidence of pulmonary tumour metastasis exhibited by knockdown of miR-296-3p in M12 when injected into athymic nude mice via tail vein, and consistently down-expression of ICAM-1 reverses this to increase extravasation of CTCs into lungs. Above results suggest that this newly identified miR-296-3p-ICAM-1 axis has a pivotal role in mediating PCa metastasis by possible enhancing survival of NK cell-resistant CTC. Our findings provide novel potential targets for PCa therapy and prognosis.
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Yan
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: C
authors.initials: C
authors.lastname: Zhu
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: M
authors.initials: M
authors.lastname: Xu
authors.forename: Q
authors.initials: Q
authors.lastname: Sun
authors.forename: R
authors.initials: R
authors.lastname: Deng
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Qu
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: B
authors.initials: B
authors.lastname: Jiang
authors.forename: J
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D015151:Immunoblotting; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D007694:Killer Cells, Natural / Q000502:physiology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs; D018799:Intercellular Adhesion Molecule-1