Mir-26 Micro RNA Precursor Family - MiR-26b Roles

MiR-26b Roles

Hypoxia

miR-26 is involved in responses to low oxygen levels and has been shown to suppress cell apoptosis in a hypoxia environment. A proposed mechanism for this is the direct targeting of proapoptotic protein BAK1 by miR-26.

Neuronal differentiation

The expression of genes which, upon activation, induce neural stem cell differentiation into neurons are suppressed by a group of phosphatases known as polymerase II carboxy-terminal domain small phosphatases (CTDSPs). Alongside other phosphatases, CTDSPs make up important components of a REST (repressor element 1 silencing transcription factor)/NRSF (neuron-restrictive silencer factor) protein complex. This REST/NRSF complex controls activation of the genes in turn responsible for control of neural stem cell differentiation. miR-26b, encoded in an intron of the CTDSP2 primary transcript, has been found to target and repress expression of CTDSP2. Mature miR-26b generation is activated during neurogenesis and there is an inactive negative feedback loop in place between miR-26b and CTDSP2 in neuronal stem cells, with inhibition of miR-26b at the precursor level.

Hepatocellular carcinoma

miR-26a/b function synergistically with their host genes, CTDSPL, CTDSP2 and CTDSP1,to block G1/S transition by activating the pRb protein in MHCC-97L,HepG2 and Huh7 liver cancer cells. Patients whose tumors have low miR-26 expression have shorter overall survival but a better response to interferon α therapy than do patients whose tumors have high expression of the microRNA.

Nasopharyngeal epithelial (CNE) cells

miR-26b is more than 38 fold downregulated in carcinoma of nasopharyngeal epithelia (CNE) cells under desferrioxamine(DFOM) induced hypoxia condition.The expression levels of miR-26b and COX-2 protein are inversely correlated in DFOM-treated CNE cells.Overexpression of miR-26b in DFOM-treated CNE cells inhibits cell proliferation through targeting COX-2.

Breast cancer

miR-26b plays a protective role in the molecular etiology of human breast cancer by promoting apoptosis.Expression of miR-26b is decreased in human breast cancer and seven human breast cancer cell lines, MCF7, HCC1937, MDA-MB-231, MDA-MB-468,MDA-MB-453, BT-549 and BT-474.Overexpression of miR-26b impairs viability and triggers apoptosis of human breast cancer MCF7 cells. SLC7A11 is identified as a direct target of miR-26b and its expression is remarkably increased in both breast cancer cell lines and clinical samples.

Colorectal cancer

The expression of miR-26b is significantly decreased in the embryonic stem cell line HUES-17s and colorectal cancer (CRC) cell line LoVo cells, compared with other three colorectal cell lines SW480, HT29 and Caco-2. Overexpression of miR-26b expression by miR-26 mimics transfection leads to the significant suppression of the cell growth and the induction of apoptosis in LoVo cells in vitro, and the inhibition of tumour growth in vivo.Four genes (TAF12, PTP4A1, CHFR and ALS2CR2) with intersection are the targets of miR-26b.The regulatory pathways of miR-26b are significantly associated with the invasiveness and metastasis of CRC cells.

Glioma

miR-26b may act as a tumor suppressor in glioma. Low level expression of miR-26b has been found in glioma cells. The level of miR-26b is inversely correlated with the grade of glioma. EphA2 is a direct target of miR-26b. Over-expression of miR-26b in glioma cells represses the endogenous level of EphA2 protein. Ectopic expression of miR-26b inhibits the proliferation, migration, invasion and vasculogenic mimicry of human glioma cells.

Growth-hormone (GH)-producing pituitary tumors

miR-26b has been found to directly target and regulate the expression of the PTEN tumour suppressor gene, mutations of which lead to activation of a PI3K/AKT signalling pathway, increased cell survival and an onset of oncogenesis. The regulation of PTEN by miR-26b sees direct effects of miR-26b on pituitary cell tumour behaviour, with miR-26b inhibition suppressing pituitary tumour growth in xenografts. Another microRNA, miR-128 microRNA precursor|miR-128, regulates expression of a BMI1 gene which suppresses PTEN expression levels by binding to its promoter region. Inhibition of miR-26b expression alongside upregulation of miR-128 suppresses the colony-forming ability and invasiveness of pituitary tumour cells.