title: Regulation of Cell Proliferation and Migration by miR-203 via GAS41/miR-10b Axis in Human Glioblastoma Cells.
abstract: Glioma amplified sequence 41(GAS41) is a potent transcription factor that play a crucial role in cell proliferation and survival. In glioblastoma, the expression of GAS41 at both transcriptional and post transcriptional level needs to be tightly maintained in response to cellular signals. Micro RNAs (miRNA) are small non coding RNA that act as important regulators for modulating the expression of various target genes. Studies have shown that several miRNAs play role in the post-transcriptional regulation of GAS41. Here we identified GAS41 as a novel target for endogenous miR-203 and demonstrate an inverse correlation of miR-203 expression with GAS41 in glioma cell lines (HNGC2 and U87). Over expression of miR-203 negatively regulates GAS41 expression in U87 and HNGC2 cell lines. Moreover, miR-203 restrained miR-10b action by suppressing GAS41. GAS41 is essential for repressing p53 in tumor suppressor pathway during cell proliferation. Enforced expression of GAS41 produced contradictory effect on miR-203 but was able to enhance p53 tumor suppressor pathway associated protein. It was also found that miR-203 maintains the stability of p53 as knock down of p53 expression using siRNA resulted in down regulation of pri-miR and mature miR-203 expression. Conversely reconstitution of miR-203 expression induced apoptosis and inhibited migratory property of glioma cells. Taken together, we show that miR-203 is a key negative regulator of GAS41 and acts as tumor suppressor microRNA in glioma.
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500007, India.|Academy of Scientific and Innovative Research, Arunasafali Marg, New Delhi, 110025, India.
authors.forename: Dhananjaya
authors.initials: D
authors.lastname: Pal
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500007, India.
authors.forename: Debasmita
authors.initials: D
authors.lastname: Mukhopadhyay
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500007, India.|School of Chemical and Biotechnology, SASTRA University, Tirumalaisamudram, Thanjavur, 613401, India.
authors.forename: M Janaki
authors.initials: MJ
authors.lastname: Ramaiah
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500007, India.|Functional Genomics and Gene silencing group, CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500007, India.
authors.forename: Pranjal
authors.initials: P
authors.lastname: Sarma
authors.affiliation: Functional Genomics and Gene silencing group, CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500007, India.
authors.forename: Utpal
authors.initials: U
authors.lastname: Bhadra
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500007, India.|Academy of Scientific and Innovative Research, Arunasafali Marg, New Delhi, 110025, India.
authors.forename: Manika Pal
authors.initials: MP
authors.lastname: Bhadra
mesh_terms: D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C547183:MIRN10 microRNA, human; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C109446:YEATS4 protein, human; D016283:Proto-Oncogene Proteins p21(ras)