miRNA expression profiles in chronic lymphocytic and acute lymphocytic leukemia

Abstract

MicroRNAs (miRNAs) are a class of small endogenous RNAs that play important regulatory roles by targeting mRNAs for cleavage or translational repression. miRNAs act in diverse biological processes including development, cell growth, apoptosis, and hematopoiesis, suggesting their association with cancer. We determined the miRNA expression profile of chronic and acute lymphocytic leukemias (CLL and ALL) using the TaqMan ® MicroRNA Assays Human Panel (Applied Biosystems). Pooled leukemia samples were compared to pooled CD19 + samples from healthy individuals (calibrator) by the 2 -∆∆Ct method. Total RNA input was normalized based on the Ct values obtained for hsa-miR-30b. The five most highly expressed miRNAs were miR-128b, miR-204, miR-218, miR-331, and miR181b-1 in ALL, and miR-331, miR-29a, miR-195, miR-34a, and miR29c in CLL. To our knowledge, this is the first report associating miR128b, miR-204 and miR-331 to hematological malignancies. The miR-17-92 cluster was also found to be up-regulated in ALL, as previously reported for some types of lymphomas. The differences observed in gene expression levels were validated for miR-331 and miR-128b in ALL and CD19 + samples. These miRNAs were upregulated in ALL, in agreement with our initial results. A brief target analysis was performed for miR-331. One of its putative targets, SOCS1, promotes STAT activation, which is a known mediator of cell proliferation and survival, suggesting the possibility of an association between miR-331 and these processes. This initial screening provided information on miRNA differentially expressed in normal and malignant B-cells that could suggest the potential roles of these miRNAs in hematopoiesis and leukemogenesis.

Serum miR-195 is a diagnostic and prognostic marker for osteosarcoma

“…For example, Zhao et al [16] reported that serum miR-195 was downregulated in breast cancer and was a potential marker for the diagnosis of this disease; Guo et al [17] demonstrated a tumor suppressive role of miR-195 in nonesmall cell lung cancer; Wang et al [18] indicated that miR-195 had a suppressive role in colorectal cancer and was able to inhibit cancer cell proliferation, colony-formation, and invasion. In contrast, Zanette et al [27] using the TaqMan miRNA assays identified miR-195 as one of highly expressed miRNAs in chronic lymphocytic leukemias. In the present study, our data showed the decreased serum miR-195 expression in osteosarcoma patients and confirmed its significant associations with aggressive clinicopathologic features including advanced clinical stage and positive distant metastasis, suggesting its tumor suppressive role in this cancer.…”

The miRNA expression profile of the uveal melanoma

“…This was possibly because they chose a cell strain of uveal melanoma to test miRNA, instead of directly using the human uveal melanoma and normal uveal tissues as we did in our experiment. Zanatte et al [13], when constructing the expression profile of miRNA for CLL, saw an up-regulation in miRNA-34a. We therefore speculated that in different types of tumor, the regulation method on the target gene by miRNA might vary, where different signal pathways or different checkpoints of a signal pathway might be involved.…”

MiR-34a promotes Fas-mediated cartilage endplate chondrocyte apoptosis by targeting Bcl-2

“…miR-34a is also induced by p53, leading to cell apoptosis or cell cycle arrest [23][24][25]. Its abnormal expression is correlated with several human diseases including cancer and leukemia [23,26,27]. It is reported that silencing of miR-34a by miR-34a-specific locked nucleotide analogs (LNAs) could reduce the apoptosis induced by DNA damage [25].…”