Mir-181 Micro RNA Precursor - MiR-181 Roles

MiR-181 Roles

Chronic Lymphocytic Leukemia
miR-181 may have a regulatory role with tumor suppressors genes of the human chromosome 1. It has been shown that the Tcl1 oncogene is a target of miR-181a in an inhibition relation (downregulated) that would result in an action on the tumor cell growth process. miR-181 expression has a reverse correlation with Tcl1 protein expression.

Myoblast Differentiation
It has been shown that miR-181 targets the homeobox protein Hox-A11 and participates in establishing muscle tissue downregulating it (a repressor of the differentiation process in mammalians and lower organisms).

Breast cancer
miR-181a, miR-181b, miR-181c and miR-181d are activated by the human gene ERBB2, located on the chromosome 17. The expression of miR-181c is relevant to characterize a Breast cancer form, the HER2/neu.
miR-181 is also activated by the small molecule tamoxifen. One selective modulators of estrogen receptor having specific activities of tissue. Tamoxifen acts as an anti-estrogen (inhibitor) in breast tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and the proliferation of endometrial cells. miR-181 could acquire a resistance to tamoxifen, the drug is successfully used to treat women with estrogen receptor-positive breast cancer.

Acute Myeloid Leukemia
Downregulation of miR-181 family contributes to aggressive leukemia phenotype through mechanisms related to the activation pathways of innate immunity mediated by toll-like receptors TLR2, TLR4, TLR7 and TLR8 and interleukin-1β IL1B (humans on chromose 2).

Glioblastoma
miR-181a, miR-181b, and miR-181c, which are down-regulated in glioblastoma. miR-181b is downregulated in glioma samples compared with the normal brain tissue. It is suggested that the downregulation of miR-181 may play a role in the development of cancer. It is shown that transfection of miR-181a and miR-181b triggers growth inhibition, apoptosis and inhibits invasion. In addition, the expression of miR-181a was found to be inversely correlated with tumor grading while miR-181b was uniformly downregulated in gliomas with different grades of malignancy.

Glioma
It has been shown that downregulated miR-181a and miR-181b were also involved in the oncogenesis of gliomas. miR-181a and miR-181b function as tumor suppressors that cause inhibition of growth, induce apoptosis and inhibit invasion of glioma cells. In addition, the tumor suppressive effect of miR-181b in glioma cells was apparent that the effect of miR-181a. These aberrant results suggest that downregulated miR-181a and miR-181b may be key factors that contribute to the occurrence in malignant human gliomas.

Multiple Myeloma
MiRNA signature for multiple myeloma (MM) has been described, including miR-181a and miR-181b, which modulate the expression of proteins essential for the pathogenesis of myeloma. Xenograft studies using human MM cell lines treated with miR-181a and miR-181b antagonists resulted in significant suppression of tumor growth in nude mice.

Papillary Thyroid Carcinoma
It was found that miR-181a and miR-181c are overexpressed in Papillary Thyroid Carcinoma tumors, sufficiently to successfully predict cancer status.

Hepatocellular Carcinoma
It has been shown that conserved miR-181 family were upregulated in EpCAM+ AFP+ Hepatocellular Carcinoma (HCC) cells and EpCAM+ HCC isolated from AFP+ tumors. In addition, miR-181 family members were highly expressed in the embryonic liver and isolated hepatic stem cells. Especially, inhibition of miR-181 leads to a reduction of the EpCAM+, the amount of HCC cells and initiate tumor capacity, whereas exogenous miR-181 expression in HCC cells resulted in an enrichment of EpCAM+ HCC cells. miR-181 could directly target hepatic transcriptional regulators of differentiation (like homeobox 2 CDX2 and 6 GATA proteins binding GATA6) and an inhibitor of Wnt / beta-catenin. It suggests that miR-181 may eradicate HCC.