title: Gas5 Exerts Tumor-suppressive Functions in Human Glioma Cells by Targeting miR-222.
abstract: Aberrant expression of noncoding RNAs in glioma cells, including long noncoding RNAs (lncRNAs) and microRNAs, may participate in the progression of glioma. Encoded by Growth Arrest-Specific 5 (GAS5) gene, lncRNA Gas5 was reported to be a negative regulator for survival and proliferation of several cancers. Here, Gas5 is found to be downregulated in glioma specimens and U87 and U251 glioma cell lines. We showed that the introduction of Gas5 by plasmid transfection increased the expression of tumor suppressor Bcl-2-modifying factor (bmf) and Plexin C1 via directly targeting and reducing the expression of miR-222. Downregulated expression of miR-222 inhibited U87 and U251 cell proliferation and promoted the apoptosis by upregulating bmf. As downstream signaling molecules of bmf, Bcl-2 and Bax were involved in the process. Meanwhile, knockdown of miR-222 attenuated U87 and U251 cell migration and invasion by upregulating Plexin C1, and cofilin was a crucial regulator targeted by Plexin C1. Gas5 combined with the knockdown of miR-222 resulted in the smallest tumor volumes and the longest survivals of nude mice in vivo. In summary, we show that Gas5 suppresses tumor malignancy by downregulating miR-222, which may serve as a promising therapy for glioma.
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People's Republic of China.
authors.forename: Xihe
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People's Republic of China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People's Republic of China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005910:Glioma / Q000235:genetics* / Q000628:therapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D011991:Receptors, Virus; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C486655:BMF protein, human; C561567:GAS5 long non-coding RNA, human; C525710:MIR222, human; C112038:VESPR semaphorin receptor