| Entity | Human neoplasms. |
| Note | Overexpression was fist shown in glioblastoma and then in papillary thyroid carcinoma (PTC), breast tumors and other various tumors (e.g. colorectal carcinoma, lung tumors, pancreatic tumors, prostate tumors, stomach tumors cholangiocarcinomas, neuroblastoma, hepatocellular carcinoma and uterine leiomyomas) and cervical adenocarcinoma cell line, HeLa. Relatively low expression was seen in cell lines HL-60 (promyelocytic leukemia), K562 (chronic myelogenous leukemia) and prostatic adenocarcinoma cell line. miRNA microarray data from 540 samples from 6 solid cancers (lung, stomach, prostate, colon, pancreatic and breast) showed overexpression of MIRN21 gene compared to normal cells. |
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| Entity | Glioblastoma |
| Disease | Overexpression of MIRN21 was first shown in malignant human brain tumor cells. When, human glioblastoma tumor tissues, 12 early passage cultures (passage 3) from high grade gliomas and 6 glioblastoma cell lines (A172, U87, U373, LN229, LN428 and LN308) were compared to non-neoplastic glial cells and a variety of mammalian tissues, MIRN21 was found to be strongly overexpressed in the neoplastic samples. Moreover, oligonucleotide microarrays specific for 180 human and mouse miRNAs and Northern blotting methods were used to profile expression of MIRN21.In glioblastoma tissues its expression showed 5 to 100 fold increase compared to non-neoplastic brain sample and 5 to 30 fold increase in cell lines compared to normal. |
| Oncogenesis | Apoptosis: Loss-of-function approach was used to identify the biological significance of MIRN21 in glioblastoma cells. Sequence specific inhibitors (2¹-O-methyl-oligonucleotides) were used to knock-down MIRN21 transcript and apoptosis activity (caspase-3 and caspase-7 enzymatic activities) was measured. 48 hours post-transfection, caspase activity increased 3-folds suggesting that MIRN21 acted as an anti-apoptotic factor in glioblastoma cells through blocking expression of key apoptosis-enabling genes. |
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| Entity | Breast Cancer. |
| Disease | RNAs from 76 breast cancer tumors and 14 cell lines were analyzed by using miRNA microarray and Northern blotting (10 normal samples were used for comparison and normalization). MIRN21 was up-regulated and the results were confirmed by Northern blotting. Consistent with other studies, MIRN21 overexpression in breast tumors compared to matched normal breast tissues was verified by stem-loop RT real-time PCR and miRNA microarrays containing 157 mature human miRNAs. |
| Oncogenesis | Apoptosis: Inhibition of MIRN21 in breast cancer cell line MCF-7 by transfection of anti-mir-21 inhibitors (chemically modified oligonucleotides) showed growth inhibition. Treatment of transfected MCF-7 cell line with anticancer drug topotecan (TPT) caused cell growth inhibition by 40%. The results suggested suppression of MIRN21 gene could sensitize tumor cells to anticancer drugs. Inhibition of MIRN21 in a xenograft carcinoma mouse model verified tumor growth suppression. Transfection results of MCF-7 cells with a general caspase inhibitor suggested MIRN21 role in regulation of bcl-2 gene expression indirectly, possibly controlling expression of genes involved in apoptosis pathways including bcl-2. |
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| Entity | Pancreatic cancer. |
| Disease | 16 pancreatic adenocarcinomas and 10 adjacent benign tissues compared to 6 normal pancreas samples were analyzed for MIRN21 precursor expression and compared to mature MIRN21 by using real-time PCR assay. The results were consistent between precursor and mature MIRN21 showing overexpression. |
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| Entity | Neuroblastoma. |
| Disease | Neuroblastoma cell line, SH-SY5Y, was treated with a tumor promoting agent (12-O-tetradecanoyl phorbol 13-acetate (TPA)) to induce differentiation into a neuronal phenotype. Following stimulation, microarray analysis of stem-loop precursors was performed and MIRN21 showed 7-8 times higher expression compared to other up-regulated miRNAs showing 2-4 times relative increase. |
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| Entity | Lung cancer. |
| Disease | Analysis of 104 pairs of primary lung cancers and non-cancerous lung tissues by microRNA microarray showed differential expression of mature MIRN21 among phenotypical and histological classifications. The results were confirmed by solution hybridization and RT-PCR. The results verified up-regulation of MIRN21 in lung cancer tissues compared to normals. Moreover, real time RT-PCR results for stem-loop precursor of MIRN21 showed at least 2-fold up-regulation in 66% of 32 cases. |
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| Entity | Other cancers. |
| Disease | In other miRNA microarray studies, MIRN21 was found to be overexpressed in papillary thyroid cancer, hepatocellular carcinoma, cholangiocarcinomas and uterine leiomyomas. A study suggested that MIRN21 inhibition in a cervical adenocarcinoma cell line, HeLa, caused increase in cell growth. |
| Prognosis | MIRN21 (as well as 7 other miRNAs) expresion was correlated with adenocarcinoma patients¹ survival. Patients that have high expression of MIRN21 were found to have worse prognosis. Thus, in addition to potential role of MIRN21 in lung carcinogenesis through apoptosis pathway, it was suggested that expression profiles could be informative in adenocarcinoma patient survival. |
| Cytogenetics | Genomic amplification of chromosome band 17q23.2 in neuroblastoma, breast cancer, colon cancer, lung cancer is known. |
| Oncogenesis | Apoptosis: MIRN21 was found to be highly over-expressed in malignant cholangiocytes. In cholangiocarcinoma cells it was shown that one of the targets of MIRN21 was PTEN encoding phosphatase that inhibited the survival and growth promoting activity of PI 3-kinase (phosphoinositole 3-kinase) signaling. In another report, inhibiton of MIRN21 showed increased sensitivity to gemcitabine. The results suggested that MIRN21 regulated gemcitabine-induced apoptosis by PTEN (phosphatase and tensin homolog) dependent activation of PI 3-kinase and AKT/mTOR signaling. These studies suggested anti-apoptotic role for the MIRN21 gene. |
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