title: miR-29s inhibit the malignant behavior of U87MG glioblastoma cell line by targeting DNMT3A and 3B.
abstract: miR-29s (including miR-29a-c) have been confirmed to be effective tumor suppressors for a variety of malignant tumors including glioblastoma. Promoter hypermethylation resulting from DNMT3A and 3B overexpression is an important epigenetic mechanism for tumor suppressive gene silencing. Bioinformatics predicts both DNMT3A and 3B are targets of miR-29s, but the anti-glioblastoma effects of miR-29s induced DNMT3A/3B downregulation deserve further investigation. We herein demonstrated that miR-29s effectively blocked DNMT3A and 3B expression by degrading their mRNAs in U87MG glioblastoma cell line. Exogenous miR-29s substantially inhibited the proliferation, migration and invasion of U87MG cells, and promoted their apoptosis. These effects could be perfectly mimicked by a small interfering RNA against DNMT3A and 3B, and partially compromised by DNMT3A/3B expression plasmids co-transfection, suggesting that miR-29s exerted the above tumor suppressive effects at least partly by silencing DNMT3A/3B. These findings provide a rationale for miR-29s based therapeutic strategies against glioblastoma.
authors.affiliation: Department of Neuropathology, Tianjin Neurologic Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Neuropathology, Tianjin Neurologic Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Neuropathology, Tianjin Neurologic Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors.forename: Cuijuan
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Neuropathology, Tianjin Neurologic Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors.forename: Cuiyun
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Biochemistry, Basic Medical College of Tianjin Medical University, Tianjin 300070, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Neuropathology, Tianjin Neurologic Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Department of Neuropathology, Tianjin Neurologic Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China; Laboratory of Hormone and Development, Ministry of Health, Institute of Endocrinology, Tianjin Medical Univeristy, Tianjin 300070, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Neuropathology, Tianjin Neurologic Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neuropathology, Tianjin Neurologic Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors.forename: Jinling
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Neuropathology, Tianjin Neurologic Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors.forename: Huining
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neuropathology, Tianjin Neurologic Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors.forename: Tongling
authors.initials: T
authors.lastname: An
authors.affiliation: Department of Neuropathology, Tianjin Neurologic Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors.forename: Xuexia
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Neuropathology, Tianjin Neurologic Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Neuropathology, Tianjin Neurologic Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China. Electronic address: wangqiantni@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Neuropathology, Tianjin Neurologic Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China. Electronic address: tjyushizhu@yahoo.com.
authors.forename: Shizhu
authors.initials: S
authors.lastname: Yu
mesh_terms: D017209:Apoptosis; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D000090205:DNA Methyltransferase 3A; D015870:Gene Expression; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D035683:MicroRNAs; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C532045:MIRN29a microRNA, human
keywords: Apoptosis; DNA methyltransferase; Glioblastoma; Invasion; Proliferation; miR-29 family