title: CD44 is a direct target of miR-199a-3p and contributes to aggressive progression in osteosarcoma.
abstract: Osteosarcoma is the most common primary bone malignancy in children and adolescents. Herein, we investigated the role of cluster of differentiation 44 (CD44), a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion, and migration in osteosarcoma. We constructed a human osteosarcoma tissue microarray with 114 patient tumor specimens, including tumor tissues from primary, metastatic, and recurrent stages, and determined the expression of CD44 by immunohistochemistry. Results showed that CD44 was overexpressed in metastatic and recurrent osteosarcoma as compared with primary tumors. Higher expression of CD44 was found in both patients with shorter survival and patients who exhibited unfavorable response to chemotherapy before surgical resection. Additionally, the 3'-untranslated region of CD44 mRNA was the direct target of microRNA-199a-3p (miR-199a-3p). Overexpression of miR-199a-3p significantly inhibited CD44 expression in osteosarcoma cells. miR-199a-3p is one of the most dramatically decreased miRs in osteosarcoma cells and tumor tissues as compared with normal osteoblast cells. Transfection of miR-199a-3p significantly increased the drug sensitivity through down-regulation of CD44 in osteosarcoma cells. Taken together, these results suggest that the CD44-miR-199a-3p axis plays an important role in the development of metastasis, recurrence, and drug resistance of osteosarcoma. Developing strategies to target CD44 may improve the clinical outcome of osteosarcoma.
authors.affiliation: 1] Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 [2] Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
authors.forename: Jacson K
authors.initials: JK
authors.lastname: Shen
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
authors.forename: Min
authors.initials: M
authors.lastname: Lin
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
authors.forename: Edwin
authors.initials: E
authors.lastname: Choy
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Cote
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
authors.forename: David C
authors.initials: DC
authors.lastname: Harmon
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Mankin
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Hornicek
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Duan
mesh_terms: D020413:3' Untranslated Regions; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D001665:Binding Sites; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D020413:3' Untranslated Regions; D018960:Hyaluronan Receptors; D035683:MicroRNAs; D012333:RNA, Messenger; C531408:mirn199 microRNA, human