RGD Reference Report - A Feedback Loop between MicroRNA 155 (miR-155), Programmed Cell Death 4, and Activation Protein 1 Modulates the Expression of miR-155 and Tumorigenesis in Tongue Cancer. - Rat Genome Database

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A Feedback Loop between MicroRNA 155 (miR-155), Programmed Cell Death 4, and Activation Protein 1 Modulates the Expression of miR-155 and Tumorigenesis in Tongue Cancer.

Authors: Zargar, Shabir  Tomar, Vivek  Shyamsundar, Vidyarani  Vijayalakshmi, Ramshankar  Somasundaram, Kumaravel  Karunagaran, Devarajan 
Citation: Zargar S, etal., Mol Cell Biol. 2019 Mar 1;39(6). pii: MCB.00410-18. doi: 10.1128/MCB.00410-18. Print 2019 Mar 15.
RGD ID: 21081517
Pubmed: PMID:30617160   (View Abstract at PubMed)
PMCID: PMC6399668   (View Article at PubMed Central)
DOI: DOI:10.1128/MCB.00410-18   (Journal Full-text)

MicroRNA 155 (miR-155) is an oncomir, generated as a noncoding RNA from the BIC gene whose promoter activity is mainly controlled via activation protein 1 (AP-1) and NF-κB transcription factors. We found that the expression levels of miR-155 and programmed cell death 4 (Pdcd4) exhibit inverse relationships in tongue cancer cells (SAS and AWL) and tumor tissues compared to their relationships in normal FBM cells and normal tongue tissues, respectively. In silico and in vitro studies with the 3' untranslated region (UTR) of Pdcd4 via luciferase reporter assays, quantitative PCR (qPCR), and Western blotting showed that miR-155 directly targets Pdcd4 mRNA and blocks its expression. Ectopic expression of Pdcd4 or knockdown of miR-155 in tongue cancer cells predominantly reduces AP-1-dependent transcriptional activity of the BIC promoter and decreases miR-155 expression. In this study, we demonstrate that miR-155 expression is modulated by a feedback loop between Pdcd4, AP-1, and miR-155 which results in enhanced expression of miR-155 with a consequent progression of tongue tumorigenesis. Further, miR-155 knockdown increases apoptosis, arrests the cell cycle, regresses tumor size in xenograft nude mice, and reduces cell viability and colony formation in soft-agar and clonogenic assays. Thus, the restoration of Pdcd4 levels by the use of molecular manipulation such as using a miR-155 sponge has an essential role in the therapeutic intervention of cancers, including tongue cancer.



Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Mir155  (microRNA 155)

Genes (Mus musculus)
Mir155  (microRNA 155)

Genes (Homo sapiens)
MIR155  (microRNA 155)


Additional Information