2q31.1

MIRN10B,hsa-mir-10b,miRNA10B,mir-10b

Colorectal neoplasia

Possible changes in microRNA levels; including miR-10b, was investigated during colorectal tumorigenesis. There was not a significant down-regulation of microRNA 10b in colon tumors to suggest a potential role in colorectal tumorigenesis.

Breast Cancer

76 breast cancers and 10 normal breast samples were analyzed by microRNA microarray and Northern Blotting to identify miRNAs whose expression is deregulated notably in cancer versus normal breast tissues. According to these results; miR-10b was one of the microRNAs which were down-regulated.

Tumor invasion and Metastasis: Although miR-10b was downregulated in nonmetastatic breast cancers in comparison with normal breast tissue, this miRNA was over-expressed in about 50% of metastatic breast cancers. Ectopic expression of miR-10b had no effect on proliferation, but an increase in transwell migration and Matrigel invasion was observed. In vivo ectopic expression of miR-10b conferred invasive properties on otherwise non-invasive breast cancer cells. Although control tumors could not invade surrounding tissues and exhibited poor vascularization, miR-10b over-expressing tumors exhibited an invasive behavior and were highly vascularized. miR-10b promoted metastasis in non-metastatic breast cancer cells. Lung micro-metastasis was detected in miR-10b over-expressing cells while there were no intravasating cells or lung metastases in control tumors.
It was shown that miR-10b expression was induced by transcription factor TWIST allowing miR-10b to inhibit translation of the mRNA encoding homeobox D10 (Figure 2). This resulted in increased expression of a well-characterized prometastatic gene, RHOC (ras homolog gene family member C), thus leading to migration, tumor invasion, and metastasis.

Glioblastoma

miR-10b was one of the over-expressed miRNAs in glioblastomas compared to peripheral tissues. According to the microarray studies on glioblastomas, an excess of 1.97- to 13.6-fold increase was observed in 5 in out of 9 samples. This data was further confirmed by Northern blotting. miR-10b was stated to be a candidate oncogene microRNA as it was significantly upregulated in glioblastomas.

Role of microRNAs in the biology of NPMc+ (nucleophosmin) AML was investigated in 85 adult de novo AML patients. Microarray studies characterized these patients for subcellular localization/mutation status of NPM1 and FLT3 mutations. A strong microRNA expression pattern was identified which differentiated NPMc+ mutated from the cytoplasmic-negative (NPM1 unmutated) cases. According to this pattern, miRNA-10b together with miRNA-10a, let-7 and miR-29 family members were up-regulated. These data was further confirmed by qRT-PCR in 44 AML patients (randomly chosen from the initial cohort). According to the overall results, it was remarkable that miRNA-10b and miRNA-10a expression levels clearly differentiated NPMc+ vs. NPMc- cases.

Central Nervous System (CNS) tumors

Although, miRNA-10b was not specifically expressed in brain tissue, it was one of the 5 microRNAs which were highly expressed in CNS tumor-derived cell lines compared to normal brain tissue.

Hepatocellular adenomas (HCAs) and Hepatocellular Carcinomas (HCCs)

Expression of miRNAs was analyzed in a series of 46 malignant and benign hepatocellular tumors compared to 4 normal liver tissues. The most significant deregulated miRNAs were further analyzed in a second series of 43 tumors and 16 non-tumor liver tissues including cirrhosis and chronic hepatitis of various etiologies. miRNA-10b was found to be overexpressed in HCC when compared to benign tumors and non-tumor liver tissues.

Protein synthesis inhibition

The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or A3G) and other APOBEC family members were shown to induce protein synthesis by miRNAs such as miR-10b in 293T and HeLa cells. miRNA microarray results suggested overexpression of miR-10b in 293T cells. Luciferase assay showed A3G effects on miRNA mediated translational repression. A3G facilitates recruitment of miRNA-targeted mRNA to polysomes to synthesize more proteins and drives dissociation of miRNA-targeted mRNA from P-bodies.

Megakaryocytopoiesis

In order to discover regulatory pathways during megakaryocytic differentiation, microRNA expression profiling was performed for in vitro differentiated megakaryocytes derived from CD34+ hematopoietic progenitors. According to the PAM (predictive analysis of microarray), miR-10b was one of the microRNAs which were identified to be involved in megakaryocytic differentiation. Downregulation of miR-10b was shown by microarrays. But Northern blot analysis and q-RT-PCR results showed that miR-10a and miR-130a were the most significantly down-regulated among the examined miRNAs.

Adipogenesis

miR-10b was shown to be up-regulated during 3T3-L1 pre-adipocyte differentiation. It was stated that this up-regulation may not be related to an actual differentiation process and may be induced by growth arrest and/or hormonal stimulation.