The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers. Export

@article{citeulike:3721747, abstract = {MicroRNAs (miRNA/miR) are a class of small noncoding RNAs implicated in the pathogenesis of various malignancies. In the current study, using micro(RNA) arrays, we found a ubiquitous loss of miR-126 expression in colon cancer lines when compared to normal human colon epithelia. Reconstitution of miR-126 in colon cancer cells resulted in a significant growth reduction as evidenced in clonogenic assays. A search for miR-126 gene targets revealed p85beta, a regulatory subunit involved in stabilizing and propagating the phosphatidylinositol 3-kinase (PI3K) signal, as one of the potential substrates. Restoration of miR-126 in cancer cells induced a > or =3-fold reduction in p85beta protein levels, with no concomitant change in p85alpha, a gene that is functionally related to p85beta but not a supposed target of miR-126. Additionally, using reporter constructs, we show that the p85beta-3' untranslated region is directly targeted by miR-126. Furthermore, this miR-126 mediated reduction of p85beta was accompanied by a substantial reduction in phosphorylated AKT levels in the cancer cells, suggesting an impairment in PI3K signaling. Finally, in a panel of matched normal colon and primary colon tumors, each of the tumors demonstrated miR-126 down-regulation together with an increase in the p85beta protein level. Taken together, we propose that miR-126 regulates PI3K signaling partly by targeting p85beta, and that the loss of miR-126 may provide a selective growth advantage during colon carcinogenesis.}, author = {Guo, Chunguang and Sah, Jerome F. and Beard, Lydia and Willson, James K. and Markowitz, Sanford D. and Guda, Kishore}, citeulike-article-id = {3721747}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/gcc.20596}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18663744}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18663744}, doi = {10.1002/gcc.20596}, issn = {1098-2264}, journal = {Genes, chromosomes \& cancer}, keywords = {cancer, colon\_cancer, mir-126, mirna}, month = {November}, number = {11}, pages = {939--946}, posted-at = {2009-01-10 17:20:25}, priority = {2}, title = {The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers.}, url = {http://dx.doi.org/10.1002/gcc.20596}, volume = {47}, year = {2008} }

TY - JOUR ID - citeulike:3721747 L3 - citeulike-article-id:3721747 N2 - MicroRNAs (miRNA/miR) are a class of small noncoding RNAs implicated in the pathogenesis of various malignancies. In the current study, using micro(RNA) arrays, we found a ubiquitous loss of miR-126 expression in colon cancer lines when compared to normal human colon epithelia. Reconstitution of miR-126 in colon cancer cells resulted in a significant growth reduction as evidenced in clonogenic assays. A search for miR-126 gene targets revealed p85beta, a regulatory subunit involved in stabilizing and propagating the phosphatidylinositol 3-kinase (PI3K) signal, as one of the potential substrates. Restoration of miR-126 in cancer cells induced a > or =3-fold reduction in p85beta protein levels, with no concomitant change in p85alpha, a gene that is functionally related to p85beta but not a supposed target of miR-126. Additionally, using reporter constructs, we show that the p85beta-3' untranslated region is directly targeted by miR-126. Furthermore, this miR-126 mediated reduction of p85beta was accompanied by a substantial reduction in phosphorylated AKT levels in the cancer cells, suggesting an impairment in PI3K signaling. Finally, in a panel of matched normal colon and primary colon tumors, each of the tumors demonstrated miR-126 down-regulation together with an increase in the p85beta protein level. Taken together, we propose that miR-126 regulates PI3K signaling partly by targeting p85beta, and that the loss of miR-126 may provide a selective growth advantage during colon carcinogenesis. IS - 11 JF - Genes, chromosomes & cancer SN - 1098-2264 EP - 946 TI - The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers. VL - 47 SP - 939 KW - cancer KW - colon_cancer KW - mir-126 KW - mirna AU - Guo, Chunguang AU - Sah, Jerome AU - Beard, Lydia AU - Willson, James AU - Markowitz, Sanford AU - Guda, Kishore PY - 2008/11// UR - http://dx.doi.org/10.1002/gcc.20596 ER -