7q32.2

MIRN183,miR-183,miRNA183

Various cancers

The transcription factor EGR1 is a tumor suppressor gene that is downregulated in many types of cancer. Clinically, loss the function 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. Researcher reported that EGR1 is regulated by miR-183 in multiple tumor types including synovial sarcoma, rhabdomyosarcoma (RMS), and colon cancer. Using an integrative network analysis, researchers identified that miR-183 is significantly overexpressed in these tumor types as well as in corresponding tumor cell lines. Bioinformatic analyses implied 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, these 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 significant to many tumor types.

Breast cancer

In breast cancer, miR183 is dysregulated. Its expression correlates with estrogen receptor and HER2/neu receptor expression. Overexpression of miR183 would inhibit migration of breast cancer cells. Specifically, the VIL2-coding protein ezrin was confirmed as a target of miR183 and downregulation of this protein was confirmed by immunocytochemistry. Consequently, miRNA183 may present an attractive target for therapeutic intervention in breast tumor.

Lung cancer

Lung cancer is the leading cause of cancer death. In the present study, researchers have addressed the significant role of miRNA in mediating tumor metastasis, through a screen with miRNA array, researchers found that miR183 was reversely correlated with the metastatic potential of lung cancer cells. In addition, ectopic overexpression of miR183 in highly metastatic cells could inhibit cell migration and invasion. Consistent with its cellular function, miR183 regulated the expression of many migration and invasion-related genes, including ezrin, which has a role in controlling actin cytoskeleton, cell adhesion and motility.

Hepatocellular carcinoma (HCC)

miR-183 can inhibit apoptosis in human HCC cells by repressing the PDCD4 expression, and miR-183 may play an important role in HCC development.

Development

MicroRNAs (miRNAs) constitute a class of small non-coding endogenous RNAs that downregulate gene expression by mapping to 3 untranslated region (UTR) of target messenger RNAs. They have been found to regulate developmental and physiological processes in several organs and tissues. Based on previous background, researchers have performed systematic in situ hybridizations to analyze the temporal and spatial distribution of three miRNAs (miR-96, miR-182 and miR-183) that are likely to arise from a single precursor RNA during the development and the maturation of the cochlea. Strikingly, the expression of miR-96, miR-182 and miR-183 was highly dynamic during the development of the cochlea, from the patterning to the differentiation of the main cochlear structures.