The down-regulation of miR-145 has been reported in many types of human cancer, including prostate cancer (PC), suggesting that miR-145 functions as a tumor suppressor.
Furthermore, miR-143 and miR-145 suppressed tumor sphere formation and expression of CSC markers and 'stemness' factors including CD133, CD44, Oct4, c-Myc and Klf4 in PC-3 cells.
In this study, using qRT-PCR, we examined the expression of six miRNAs (miR-21, miR-31, miR-92a, miR-101, miR-106a and miR-145) in tumors from 193 prospectively recruited patients with colorectal cancer, and associations with clinicopathological parameters and patient outcome were analyzed.
Restoration of TARBP2 activity and systemic delivery of synthetic forms of either of two of its targets, miRNA-143 or miRNA-145, inhibited ESFT CSC clonogenicity and tumor growth in vivo.
Taken together, these studies suggest that miR-145 serves as a tumor suppressor which downregulates HIF-1 and VEGF expression by targeting p70S6K1, leading to the inhibition of tumor growth and angiogenesis.
Finally, in vivo study showed that PU-PEI-mediated miR145 delivery to xenograft tumors reduced tumor growth and metastasis, sensitized tumors to chemoradiotherapies, and prolonged the survival times of tumor-bearing mice.
Here, we report microRNA-145, a tumor suppressor miRNA, can protect cardiomyocytes from hydrogen peroxide H₂O₂-induced apoptosis through targeting the mitochondrial pathway.
We observed that intracranial injection of GB-NS over-expressing miR-145 delays significantly tumor development :deriving tumors showed a significant down-regulation of NEDD9.
Functional studies involving ectopic expression of miR-145 in glioma cells had a negative impact on cell proliferation and tumor development, as well as invasion and induced apoptosis, providing further support to the concept that inactivation of miR-145 is important for glioma disease pathogenesis.
MicroRNA expression was assessed with TaqMan MicroRNA Assays. p53 exons 5 to 8 were sequenced. miR-145 was downregulated (p<0.0001) and miR-367 was upregulated (p<0.0001) in tumour compared with normal tissue.
Using TCGA analysis and real-time PCR we found that the expression of miR-145/143 cluster was downregulated in astrocytic tumors compared to normal brain specimens and in glioma cells and glioma stem cells (GSCs) compared to normal astrocytes and neural stem cells.
The reduction of miR-145 expression in PCa was correlated with higher Gleason score, advanced clinical stage, larger tumour diameter and higher prostate-specific antigen (PSA) and follow-up PSA levels.
Insulin receptor substrate-1 (IRS1) was identified as a target gene of miR-145, by which miR-145 was able to suppress cell proliferation. miR-145 suppresses cell proliferation, anchorage-independent growth, cell motility, and may serve as a tumor suppressor.
The expression of the tumor suppressive E-cadherin and miR145, on the other hand, was greatly reduced while expression of the oncogenic microRNAs: miR21, miR135a and miR135b was significantly up-regulated.
Collectively, these results suggest that as a tumor suppressor, miR-145 inhibits not only tumor proliferation, but also cell migration and invasion, and warrants further investigation.