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An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells
Published on: May 21, 2019
The Double Face of miR-708: A Pan-Cancer Player with Dissociative Identity Disorder
Jaqueline Carvalho de Oliveira1, Carolina Mathias1,2, Verônica Cristina Oliveira3
1Department of Genetics, Federal University of Paraná, Curitiba 80060-000, Brazil.
Abstract:
Over the last decades, accumulating evidence has shown tumor-dependent profiles of miR-708, being either up- or downregulated, and thus, acting as a "Janus" regulator of oncogenic pathways. Herein, its functional duality was assessed through a thorough review of the literature and further validation in silico using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. In the literature, miR-708 was found with an oncogenic role in eight tumor types, while a suppressor tumor role was described in seven cancers. This double profile was also found in TCGA and GEO databases, with some tumor types having a high expression of miR-708 and others with low expression compared with non-tumor counterparts. The investigation of validated targets using miRBase, miRTarBase, and miRecords platforms, identified a total of 572 genes that appeared enriched for PI3K-Akt signaling, followed by cell cycle control, p53, Apellin and Hippo signaling, endocrine resistance, focal adhesion, and cell senescence regulations, which are all recognized contributors of tumoral phenotypes. Among these targets, a set of 15 genes shared by at least two platforms was identified, most of which have important roles in cancer cells that influence either tumor suppression or progression. In a clinical scenario, miR-708 has shown to be a good diagnostic and prognosis marker. However, its multitarget nature and opposing roles in diverse human tumors, aligned with insufficient experimental data and the lack of proper delivery strategies, hamper its potential as a sequence-directed therapeutic.
Insights
MicroRNA-708 (miR-708) acts as a dual regulator in cancer, promoting or suppressing tumors depending on the cancer type. Its complex roles and target interactions present challenges for therapeutic development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA-708 (miR-708) exhibits context-dependent roles in cancer, acting as both an oncogene and a tumor suppressor.
- Its expression patterns vary significantly across different tumor types, contributing to its complex regulatory functions.
Purpose of the Study:
- To comprehensively review the literature and analyze in silico data regarding miR-708's dual role in various cancers.
- To identify and characterize the molecular targets and signaling pathways influenced by miR-708.
Main Methods:
- Literature review of miR-708's function in oncogenesis.
- In silico analysis using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases.
- Target gene identification and pathway enrichment analysis using miRBase, miRTarBase, and miRecords.
Main Results:
- miR-708 demonstrates oncogenic roles in 8 tumor types and tumor-suppressive roles in 7 types, consistent across literature and database analyses.
- In silico analysis revealed differential expression of miR-708 in various cancers compared to non-tumor tissues.
- Enrichment analysis identified key cancer-related pathways, including PI3K-Akt signaling and cell cycle control, regulated by 572 miR-708 targets, with 15 shared targets identified.
Conclusions:
- miR-708 functions as a "Janus" molecule in cancer, with opposing roles dependent on the tumor context.
- Identified targets and pathways provide insights into miR-708's involvement in tumoral phenotypes.
- Despite diagnostic/prognostic potential, miR-708's therapeutic application is limited by its multitarget nature and delivery challenges.
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