Regulation of CDK inhibitor p27 by microRNA 222 in breast cancer patients.

BACKGROUND: Breast cancer is the most common of all cancers and the second leading cause of cancer-related deaths among women worldwide. MicroRNAs regulate at least 60% of the human genes, including tumor suppressor genes and oncogenes, and can thereby affect cancer risk. In this study, the prognostic values of the CDK inhibitor p27 and miR-222 as biomarkers for breast cancer were evaluated. METHODS: The real-time quantitative polymerase chain reaction method was employed to measure the expression level of miR-222, whereas the serum levels of the CDK inhibitor p27 were measured via enzyme-linked immunosorbent assay. The levels were determined in sera from 110 participants representing three different groups. RESULTS: Patients with breast cancer exhibited significantly higher expression levels of miR-222 and lower levels of CDK inhibitor p27 than the control group. In addition, a statistically significant inverse correlation between miR-222 and the CDK inhibitor p27 was observed. The receiver operating characteristic curves plotted for serum p27 and miR-222 helped in significantly differentiating between breast cancer patients and controls but could not discriminate between those with stage II and stage III cancer. CONCLUSION: Thus, a significant upregulation in the serum miR-222 levels was observed in cancer patients, and a significant inverse correlation was noted between the miR-222 and CDK inhibitor p27 expression levels. These findings indicate that miR-222 may be used as a useful noninvasive screening biomarker for human breast cancer. MICROABSTRACT: Novel biomarkers for prognosis, prediction, and therapeutic purposes are essential as the prognosis and therapeutic targets of breast cancer are dependent on traditional markers, such as the tumor stage and hormonal receptor status. This study aimed to evaluate the diagnostic and prognostic values of the CDK inhibitor p27 and miR-222 in breast cancer. Our results indicated that miR-222 and the CDK inhibitor p27 may be used as noninvasive biomarkers to screen for human breast cancer but cannot discriminate between patients with early breast cancer and patients with advanced breast cancer.

miR-181b promotes hepatic stellate cells proliferation by targeting p27 and is elevated in the serum of cirrhosis patients.

MicroRNAs, as a kind of negative gene regulators, were demonstrated to be involved in many types of diseases. In this study, we found that transforming growth factor-beta 1 could induce the expression of miR-181a and miR-181b, and miR-181b increased in the much higher folds than miR-181a. Because of the important role of transforming growth factor-beta 1 in HSC activation and liver cirrhosis, we investigate the effect of miR-181a and miR-181b on HSC proliferation. The results showed that miR-181b could promote HSC-T6 cell proliferation by regulating cell cycle. Further study showed p27, the cell cycle regulator, was the direct target of miR-181b in HSC-T6 cell. But miR-181a had no effects on HSC-T6 cell proliferation and cell cycle, and did not target p27. Interestingly, miR-181b is elevated significantly in serum of liver cirrhosis cases comparing to that of normal persons, whereas miR-181a expression was in the similar level with that of normal persons. These results suggested that miR-181b could be induced by TGF-ß1 and promote the growth of HSCs by directly targeting p27. The elevation of miR-181b in serum suggested that it may be potential diagnostic biomarkers for cirrhosis. As for miR-181a, it may work in TGF-ß1 pathway by a currently unknown mechanism.

Cancer-associated carbohydrate identification in Hodgkin's lymphoma by carbohydrate array profiling.

Tumor-associated carbohydrates have potential not only as diagnostic tools but also as specific therapeutic targets. Their identification, however, has been hampered by the lack of suitable technologies. We used carbohydrate array technology to compare serum antibody (IgG and IgM) levels against 37 different carbohydrates between classical Hodgkin's lymphoma (cHL) patients and age/sex-matched healthy controls. Serum IgM levels measured by ELISA against 2 of the 5 carbohydrates identified using this technique, L-alpha-arabinose (L-Araf) and alpha-N-acetylgalactosamine (GalNAc(alpha)), were higher (F values of 11.30 and 18.27, respectively) in a cohort of cHL patients (n = 16) than either diffuse large B-cell lymphoma patients (n = 18) or control sera (n = 12). Higher anti-L-Araf IgM levels in cHL patients were associated with cytosine arabinoside treatment (p < 0.05). The GalNAc(alpha) glycotope, Tn, was found to be heterogeneously expressed in the Reed-Sternberg cells of 9/20 (45%) cHL cases, but not in malignant cells of 25 cases of lymphocyte-predominant HL or another 21 hematological disorders (291 cases) examined immunohistochemically. Tn was expressed in 41/238 (17%) classical HL cases present on a tissue microarray. Expression was associated with CD79a and LMP1 expression and negatively with p27(KIP1) expression (p < 0.05). Kaplan-Meier survival analysis revealed a trend towards improved relapse-free survival with Tn expression although this was not statistically significant (p = 0.271). We suggest that this technique could provide a powerful tool for identifying novel carbohydrates in other cancers.