|Title:||ADAM9 enhances CDCP1 protein expression by suppressing MIR-218 for lung tumor metastasis||Authors:||Chiu K.-L.
|Issue Date:||2015||Publisher:||Nature Publishing Group||Journal Volume:||5||Start page/Pages:||16426||Source:||Scientific Reports||Abstract:||
Metastasis is the leading cause of death in cancer patients due to the difficulty of controlling this complex process. MicroRNAs (miRNA), endogenous noncoding short RNAs with important biological and pathological functions, may play a regulatory role during cancer metastasis, but this role has yet to be fully defined. We previously demonstrated that ADAM9 enhanced the expression of the pro-migratory protein CDCP1 to promote lung metastasis; however, the regulatory process remains unknown. Here we demonstrate that endogenous miR-218, which is abundant in normal lung tissue but suppressed in lung tumors, is regulated during the process of ADAM9-mediated CDCP1 expression. Suppression of miR-218 was associated with high migration ability in lung cancer cells. Direct interaction between miR-218 and the 3′-UTR of CDCP1 mRNAs was detected in luciferase-based transcription reporter assays. CDCP1 protein levels decreased as expression levels of miR-218 increased, and increased in cells treated with miR-218 antagomirs. Induction of miR-218 inhibited tumor cell mobility, anchorage-free survival, and tumor-initiating cell formation in vitro and delayed tumor metastases in mice. Our findings revealed an integrative tumor suppressor function of miR-218 in lung carcinogenesis and metastasis.
|ISSN:||2045-2322||DOI:||10.1038/srep16426||metadata.dc.subject.other:||ADAM protein; ADAM9 protein, human; CDCP1 protein, human; cell adhesion molecule; leukocyte antigen; membrane protein; messenger RNA; microRNA; MIRN218 microRNA, human; small interfering RNA; tumor protein; animal; binding site; cell motion; cell survival; chemistry; disease model; gene expression regulation; genetics; human; lung tumor; metabolism; metastasis; mortality; mouse; nucleotide sequence; pathology; RNA interference; tumor cell line; xenograft; ADAM Proteins; Animals; Antigens, CD; Base Sequence; Binding Sites; Cell Adhesion Molecules; Cell Line, Tumor; Cell Movement; Cell Survival; Disease Models, Animal; Gene Expression Regulation, Neoplastic; Heterografts; Humans; Lung Neoplasms; Membrane Proteins; Mice; MicroRNAs; Neoplasm Metastasis; Neoplasm Proteins; RNA Interference; RNA, Messenger; RNA, Small Interfering
|Appears in Collections:||生理學科所|
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