MicroRNA miR-183 Functions as an Oncogene by Targeting the Transcription FactorEGR1and Promoting Tumor Cell Migration

Abstract

The transcription factor EGR1 is a tumor suppressor gene that is downregulated in many cancer types. Clinically, loss of EGR1 translates to increased tumor transformation and subsequent patient morbidity and mortality. In synovial sarcoma, the SS18-SSX fusion protein represses EGR1 expression through a direct association with the EGR1 promoter. However, the mechanism through which EGR1 becomes downregulated in other tumor types is unclear. Here, we report that EGR1 is regulated by microRNA (miR)-183 in multiple tumor types including synovial sarcoma, rhabdomyosarcoma (RMS), and colon cancer. Using an integrative network analysis, we identified that miR-183 is significantly overexpressed in these tumor types as well as in corresponding tumor cell lines. Bioinformatic analyses suggested that miR-183 could target EGR1 mRNA and this specific interaction was validated in vitro. miR-183 knockdown in synovial sarcoma, RMS, and colon cancer cell lines revealed deregulation of a miRNA network composed of miR-183-EGR1-PTEN in these tumors. Integrated miRNA-and mRNA-based genomic analyses indicated that miR-183 is an important contributor to cell migration in these tumor types and this result was functionally validated to be occurring via an EGR1-based mechanism. In conclusion, our findings have significant implications in the mechanisms underlying EGR1 regulation in cancers. miR-183 has a potential oncogenic role through the regulation of 2 tumor suppressor genes, EGR1 and PTEN, and the deregulation of this fundamental miRNA regulatory network may be central to many tumor types. Cancer Res; 70(23); 9570-80. Ó2010 AACR.

MicroRNA-183/182/96 cooperatively regulates the proliferation of colon cancer cells

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“…It has been demonstrated that miR-183, 96 and 182 act as tumor oncogenes based on their high expression levels in colon cancer tissues (21). Therefore, the present study used ASO-miRs to knockdown the expression of the miR-183/96/182 cluster.…”

Five miRNAs as Novel Diagnostic Biomarker Candidates for Primary Nasopharyngeal Carcinoma

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Identification, by systematic RNA sequencing, of novel candidate biomarkers and therapeutic targets in human soft tissue tumors

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