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Series GSE129076 Query DataSets for GSE129076
Status Public on Apr 30, 2019
Title miR-450a acts as a tumor suppressor in ovarian cancer by readjusting energy metabolism
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Dysregulation of miRNA expression is associated with multiple diseases, including cancers where they can have oncogenic or tumor suppressive function. Here we investigated the potential tumor suppressive function of miR-450a, one of the most significantly downregulated miRNAs in ovarian cancer. RNAseq analysis revealed multipe genes involved in the epithelial-to-mesenchymal transition (EMT) were suppressed by miR-450a overexpression ovarian cancer cell line A2780. Consistently, miR-450a overexpression reduced tumor migration, invasion and increased anoikis in A2780 and SKOV-3 cell lines and reduced tumor growth in ovarian xenographic model. Combining AGO-PAR-CLIP and RNAseq analysis, we identified a panel of potential miR-450a targets of which many, including TIMMDC1, MT-ND2, ACO2 and ATP5B, regulate energetic metabolism. miR-450a expression indeed decreased mitochondrial membrane potential but increased glucose uptake and viability after glutamine withdrawal, characteristics of less invasive ovarian cancer cell lines, which are also less dependent on glutamine. In summary, we propose in this work that miR-450a acts as a tumor suppressor in ovarian cancer cells by modulating targets associated with glutaminolysis, which would lead to a decrease in the production of lipids, amino acids and nucleic acids, and also inhibition of signaling pathways associated with EMT
Overall design RNA-Seq from 3 different biological samples from SKOV3 and A2780 cell lines after miR-450a overexpression; small RNA-Seq from 3 different biological from A2780 cell line after miR-450a or miR-450b overexpression; AGO 4SU-PAR-CLIP from 2 to 4 biological samples from A2780 cells lines after miR-450a overexpression.
Contributor(s) Muys BR, de Sousa JF, Plaça JR, de Araújo LF, Sarshad AA, Anastasakis DG, Wang X, Li XL, de Molfetta GA, Ramão A, Lal A, Vidal DO, Hafner M, Silva WA Jr
Citation(s) 31101765
Submission date Mar 29, 2019
Last update date Jul 30, 2019
Contact name Markus Hafner
Organization name NIH
Department NIAMS
Street address 50 South Drive
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (25)
GSM3692987 A2780_pLVX_1_RNA-Seq
GSM3692988 A2780_pLVX_2_RNA-Seq
GSM3692989 A2780_pLVX_3_RNA-Seq
BioProject PRJNA529911
SRA SRP189900

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MINiML formatted family file(s) MINiMLHelp
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Supplementary file Size Download File type/resource
GSE129076_A2780-450A_gene_exp.diff.gz 914.1 Kb (ftp)(http) DIFF
GSE129076_A2780_mature_miRNAs_relative_freq.xlsx 129.8 Kb (ftp)(http) XLSX
GSE129076_A2780_prec_miRNAs_relative_freq.xlsx 89.0 Kb (ftp)(http) XLSX
GSE129076_RAW.tar 8.6 Mb (http)(custom) TAR (of XLSX)
GSE129076_SKOV3-450A_gene_exp.diff.gz 861.5 Kb (ftp)(http) DIFF
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