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Published on: April 7, 2017
MiR-92a-2-5p suppresses esophageal squamous cell carcinoma cell proliferation and invasion by targeting PRDX2
Xiang Zhan1, Jixian Li1, Renya Zeng2
1Tumor Research and Therapy Center, Shandong Provincial Hospital, Shandong University, 250021, Jinan, Shandong, China.
Abstract:
MicroRNAs (miRNAs) can function as negative regulators of gene expression by binding to the 3'-untranslated region (3'-UTR) of target genes. The aberrant expression of miRNAs in neoplasm is extensively associated with tumorigenesis and cancer progression, including esophageal squamous cell carcinoma (ESCC). Our previous investigation has identified the oncogenic roles of Peroxiredoxin2 (PRDX2) in ESCC progression; however, its upstream regulatory mechanism remains to be elucidated. By merging the prediction results from miRWalk2.0 and miRNA differential expression analysis results based on The Cancer Genome Atlas Esophageal Carcinoma (TCGA-ESCA) database, eight miRNA candidates were predicted to be the potential regulatory miRNAs of PRDX2, followed by further identification of miR-92a-2-5p as the putative miRNA of PRDX2. Subsequent functional studies demonstrated that miR-92a-2-5p can suppress ESCC cell proliferation and migration, as well as tumor growth in subcutaneous tumor xenograft models, which might be mediated by the suppression of AKT/mTOR and Wnt3a/β-catenin signaling pathways upon miR-92a-2-5p mimic transfection condition. These data revealed the tumor suppressive functions of miR-92a-2-5p in ESCC by targeting PRDX2.
Insights
MicroRNAs (miRNAs) regulate gene expression. MiR-92a-2-5p acts as a tumor suppressor in esophageal squamous cell carcinoma (ESCC) by targeting Peroxiredoxin2 (PRDX2), inhibiting cancer progression.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression, often dysregulated in cancers like esophageal squamous cell carcinoma (ESCC).
- Peroxiredoxin2 (PRDX2) has been identified as an oncogene in ESCC, but its upstream regulators require elucidation.
Purpose of the Study:
- To identify upstream regulatory miRNAs targeting Peroxiredoxin2 (PRDX2) in esophageal squamous cell carcinoma (ESCC).
- To investigate the functional role of miR-92a-2-5p in ESCC progression and its underlying molecular mechanisms.
Main Methods:
- Bioinformatic analysis integrating miRWalk2.0 predictions and TCGA-ESCA database for miRNA identification.
- In vitro functional assays assessing ESCC cell proliferation and migration.
- In vivo tumor xenograft models to evaluate tumor growth inhibition.
- Western blot analysis to examine signaling pathway modulation (AKT/mTOR, Wnt3a/β-catenin).
Main Results:
- Eight potential miRNA candidates regulating PRDX2 were predicted, with miR-92a-2-5p identified as the primary candidate.
- miR-92a-2-5p mimic transfection significantly suppressed ESCC cell proliferation, migration, and tumor growth in vivo.
- The tumor-suppressive effects of miR-92a-2-5p were associated with the inhibition of AKT/mTOR and Wnt3a/β-catenin signaling pathways.
Conclusions:
- miR-92a-2-5p functions as a tumor suppressor in ESCC by directly targeting PRDX2.
- This study elucidates a novel regulatory mechanism of PRDX2 in ESCC, highlighting miR-92a-2-5p as a potential therapeutic target.
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