Dataset Information

Hsa-miR-139-5p expression regulates the abundance of proteins related to poor survival cancer in CAL-62 thyroid cancer cell line

ABSTRACT: We studied the impact of hsa-miR-139-5p on the protein output by means of an iTRAQ-based approach. First, we established two CAL-62 isogenic cell lines expressing either the mature hsa-miR-139-5p or a non-targeting control upon a doxycycline inducible promoter (PTRE3G-tGFP, Dharmacon). Total proteins of P-tGFP-hsa-miR139-5p untreated or treated with doxycycline (1ug/ml) for 96 and 120 hours were isolated and labeled with iTRAQ® reagent 8-plex. Two independent experiments were performed.

INSTRUMENT(S): impact

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Thyroid Cancer

SUBMITTER: Eduardo Zarzuela

LAB HEAD: Mercedes Robledo

PROVIDER: PXD011901 | Pride | 2019-08-13

REPOSITORIES: Pride

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Publications

Hsa-miR-139-5p is a prognostic thyroid cancer marker involved in HNRNPF-mediated alternative splicing.

Montero-Conde Cristina C Graña-Castro Osvaldo O Martín-Serrano Guillermo G Martínez-Montes Ángel M ÁM Zarzuela Eduardo E Muñoz Javier J Torres-Perez Rafael R Pita Guillermo G Cordero-Barreal Alfonso A Leandro-García Luis J LJ Letón Rocío R López de Silanes Isabel I Guadalix Sonsoles S Pérez-Barrios Andrés A Hawkins Federico F Guerrero-Álvarez Almudena A Álvarez-Escolá Cristina C Regojo-Zapata Rita M RM Calsina Bruna B Remacha Laura L Roldán-Romero Juan M JM Santos María M Lanillos Javier J Jordá Mireia M Riesco-Eizaguirre Garcilaso G Zafon Carles C González-Neira Anna A Blasco Maria A MA Al-Shahrour Fátima F Rodríguez-Antona Cristina C Cascón Alberto A Robledo Mercedes M

International journal of cancer 20190828 2

It is critical to identify biomarkers and functional networks associated with aggressive thyroid cancer to anticipate disease progression and facilitate personalized patient management. We performed miRNome sequencing of 46 thyroid tumors enriched with advanced disease patients with a median follow-up of 96 months. MiRNome profiles correlated with tumor-specific histopathological and molecular features, such as stromal cell infiltration and tumor driver mutation. Differential expression analysis ...[more]

PMID: 31403184

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Project description:The molecular response to hypoxia is a critical cellular process implicated in cancer, and a target for drug development. The activity of the major player, HIF1M-NM-1,M-BM- is regulated at different levels, including the transcriptional level by the Ets factor ELK3. The molecular mechanisms of this intimate transcriptional connection remain largely unknown. Whilst investigating global ELK3-chromatin interactions, we uncovered an unexpected connection that involves the microRNA hsa-miR-155-5p, a hypoxia-inducible oncomir that targets HIF1M-NM-1. One of the ELK3 chromatin binding sites, detected by Chromatin Immuno-Precipitation Sequencing (ChIP-seq) of normal Human Umbilical Vein Endothelial Cells (HUVEC), is located at the transcription start site of the MIR155HG genes that expresses hsa-miR-155-5p. We confirmed that ELK3 binds to this promoter by ChIP and QPCR. We showed that ELK3 and hsa-miR-155-5p form a double-negative regulatory loop. ELK3 depletion induced hsa-miR-155-5p expression, and hsa-miR-155-5p expression decreased ELK3 expression at the RNA level through a conserved target sequence in its 3M-bM-^@M-^Y-UTR. We further showed that the activities of hsa-miR-155-5p and ELK3 are functionally linked. Pathway analysis indicates that both factors are implicated in related processes, including cancer and angiogenesis. hsa-miR-155-5p expression and ELK3 depletion have similar effects on expression of known ELK3 target genes, and in-vitro angiogenesis and wound closure. Bioinformatic analysis of cancer RNA-seq data shows that hsa-miR-155-5p and ELK3 expression are significantly anti-correlated, as would be expected from hsa-miR-155-5p targeting ELK3 RNA. Hypoxia (0% oxygen) down-regulates ELK3 mRNA in a microRNA and hsa-miR-155-5p dependent manner. These results tie ELK3 into the hypoxia response pathway through an oncogenic microRNA and into a circuit implicated in the dynamics of the hypoxic response.M-BM- This crosstalk could be important in the development of new treatments for a range of pathologies. Examination of ELK3 DNA interactions in HUVEC cells under normal oxygen conditions

Dataset Information

Hsa-miR-139-5p expression regulates the abundance of proteins related to poor survival cancer in CAL-62 thyroid cancer cell line

Publications

Hsa-miR-139-5p is a prognostic thyroid cancer marker involved in HNRNPF-mediated alternative splicing.

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