title: miR-137 acts as a tumor suppressor in astrocytoma by targeting RASGRF1.
abstract: Astrocytoma is one of the most common primary central nervous system tumors and has both high mortality and a poor 5-year survival rate. MicroRNAs (miRNAs) play important roles in carcinogenesis by acting on multiple signaling pathways. Although we have demonstrated that miR-137 is downregulated in astrocytoma tissues, the role of miR-137 in astrocytoma still remains unknown. In the present study, we aimed to investigate the function of miR-137 and its possible target genes in astrocytoma. miR-137 was significantly downregulated in astrocytoma tissues, and its expression level was inversely correlated with the clinical stage. Restoring miR-137 was able to dramatically inhibit cell proliferation, migration, and invasion and enhance apoptosis in vitro, whereas silencing its expression inhibited these processes. By overexpressing or inhibiting miR-137 in cancer cells, we experimentally confirmed that miR-137 directly recognized the 3'-UTR (3'-untranslated region) of the RASGRF1 (Ras protein-specific guanine nucleotide-releasing factor 1) transcript and regulated RASGRF1 expression. Furthermore, an inverse correlation was observed between miR-137 levels and RASGRF1 protein levels, but not mRNA levels, in astrocytoma samples. The silencing of RASGRF1 resulted in similar effects to miR-137 restoration in cancer cells. Finally, overexpression of RASGRF1 rescued the inhibitory effects of miR-137. Taken together, our results indicate that miR-137 acts as a tumor suppressor in astrocytoma by targeting RASGRF1. These findings suggest that miR-137 may serve as a novel therapeutic target in astrocytoma treatment.
authors.affiliation: Modern Medical Research Center, Third Affiliated Hospital of Soochow University, #185 Juqian Road, Changzhou, Jiangsu, China.
authors.forename: Danni
authors.initials: D
authors.lastname: Deng
authors.affiliation: Modern Medical Research Center, Third Affiliated Hospital of Soochow University, #185 Juqian Road, Changzhou, Jiangsu, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, Third Affiliated Hospital of Soochow University, #185 Juqian Road, Changzhou, Jiangsu, China.
authors.forename: Naiyuan
authors.initials: N
authors.lastname: Shao
authors.affiliation: Department of Neurosurgery, Third Affiliated Hospital of Soochow University, #185 Juqian Road, Changzhou, Jiangsu, China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Qu
authors.affiliation: Department of Neurosurgery, Third Affiliated Hospital of Soochow University, #185 Juqian Road, Changzhou, Jiangsu, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Third Affiliated Hospital of Soochow University, #185 Juqian Road, Changzhou, Jiangsu, China.
authors.forename: Suinuan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Third Affiliated Hospital of Soochow University, #185 Juqian Road, Changzhou, Jiangsu, China. xia_xiwei@126.com.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Xia
authors.affiliation: Modern Medical Research Center, Third Affiliated Hospital of Soochow University, #185 Juqian Road, Changzhou, Jiangsu, China. yilinyang.czfph@gmail.com.|Department of Neurosurgery, Third Affiliated Hospital of Soochow University, #185 Juqian Road, Changzhou, Jiangsu, China. yilinyang.czfph@gmail.com.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Modern Medical Research Center, Third Affiliated Hospital of Soochow University, #185 Juqian Road, Changzhou, Jiangsu, China. danielzhif@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhi
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D001254:Astrocytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020666:ras-GRF1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C545567:MIRN137 microRNA, human; D035683:MicroRNAs; C513039:RASGRF1 protein, human; D020666:ras-GRF1
keywords: Apoptosis; Invasion; Migration; Proliferation; RASGRF1; miR-137