MiR-520b as a novel molecular target for suppressing stemness phenotype of head-neck cancer by inhibiting CD44

• Published in: Scientific reports Vol. 7; no. 1; pp. 2042 - 14
• Main Authors: Lu, Ya-Ching, Cheng, Ann-Joy, Lee, Li-Yu, You, Guo-Rung, Li, Yan-Liang, Chen, Hsin-Ying, Chang, Joseph T.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.05.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/100; 13/109; 13/89; 13/95; 38; 38/90; 631/67/1536/1665; 631/67/1665; 82; 96; Allografts; Animals; Antineoplastic Agents - pharmacology; Cancer; CD44 antigen; Cell Line, Tumor; Cell Movement - drug effects; Cell Movement - genetics; Cell Movement - radiation effects; Cell Proliferation; Cell Self Renewal - genetics; Cell Transformation, Neoplastic - genetics; Colonization; Epithelial-Mesenchymal Transition - drug effects; Epithelial-Mesenchymal Transition - radiation effects; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - radiation effects; Head & neck cancer; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - therapy; Humanities and Social Sciences; Humans; Hyaluronan Receptors - genetics; Hyaluronan Receptors - metabolism; Immunological tolerance; Irradiation; Liver; Malignancy; Mesenchyme; Mice; MicroRNAs - genetics; multidisciplinary; Multigene Family; Neck; Neoplasm Metastasis; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Neoplastic Stem Cells - radiation effects; Nestin; Oct-4 protein; Phenotypes; Radiation; Radiation, Ionizing; RNA Interference; Science; Science (multidisciplinary); Stem cell transplantation; Stem cells; Therapeutic applications; Tumorigenesis; Xenografts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-02058-8

Cancer stem cells preferentially acquire the specific characteristics of stress tolerance and high mobility, allowing them to progress to a therapy-refractive state. To identify a critical molecule to regulate cancer stemness is indispensable to erratically cure cancer. In this study, we identified miR-520b as a novel molecular target to suppress head-neck cancer (HNC) with stemness phenotype. MiR-520b inhibited cellular migration and invasion via the mechanism of epithelial-mesenchymal transition. It also sensitized cells to therapeutic drug and irradiation. Significantly, miR-520b suppressed spheroid cell formation, as well as reduced expressions of multiple stemness regulators (Nestin, Twist, Nanog, Oct4). The CD44 molecule was identified as a direct target of miR-520b, as shown by the reverse correlative expressions, the response to miR-520 modulation, the luciferase reporter assay, and the functional rescue analyses. These cellular results were confirmed by a tumor xenograft mice study. Administration of miR-520b dramatically restrained tumorigenesis and liver colonization. Conversely, miR-520b silencing led to an acceleration of tumor growth. Taken together, our study demonstrated that miR-520b inhibits the malignancy of HNC through regulation of cancer stemness conversion by targeting CD44. MiR-520b may serve as an emerging therapeutic target that may be further developed for the intervention of refractory HNC.