miR 181a
Shi et al., showed that hsa-miR-181a and hsa-miR-181b functioned as tumor suppressors which triggered growth inhibition, induced apoptosis and inhibited invasion in glioma cells. Furthermore, the tumor-suppressive effect of hsa-miR-181b in glioma cells was more apparent than the effect of hsa-miR-181a. These findings suggest aberrantly down-regulated hsa-miR-181a and hsa-miR-181b may be critical factors that contribute to malignant appearance in human gliomas 1).
ATP2B2 target gene could be regulated by has-mir-181a to involve in calcium signaling pathway 2).
Ma et al., identified microRNA-181a (miR-181a) as a critical MicroRNA in opening BTB. MicroRNA-181a expression was upregulated in glioma endothelial cells (GECs), which were obtained by coculturing endothelial cells (ECs) with glioma cells. Overexpression of miR-181a resulted in an impaired and permeability increased BTB, and meanwhile reduced the expression of zonula occluden (ZO)-1, occludin, and claudin-5. Kruppel-like factor 6 (KLF6), a transcription factor of the zinc-finger family, was downregulated in GECs. Mechanistic investigations defined it as a direct and functional downstream target of miR-181a, which was involved in the regulation of BTB permeability and the expression of ZO-1, occludin, and claudin-5. Furthermore, luciferase assays and chromatin immunoprecipitation assays showed that KLF6 upregulated the promoter activities and interacted with the promoters of ZO-1, occludin, and claudin-5 in GECs. Collectively, we showed the possibility that overexpression of miR-181a contributes to the increased permeability of BTB by targeting KLF6, thereby revealing potential therapeutic targets for the treatment of brain gliomas 3).
Wu et al., identified miR 181a, which may have a biological function, particularly during the early stages after nerve allotransplantation under FK506 immunosuppression 4).
In HMOX1-transfected astrocytes, rno-miR-140*, rno-miR-17, and rno-miR-16 were significantly up-regulated, and rno-miR-297, rno-miR-206, rno-miR-187, rno-miR-181a, rno-miR-138 and rno-miR-29c were down-regulated, compared to sham-transfected controls 5).
Sharma et al., measured six downstream MicroRNA targets of EZH2 and found significant downregulation of four (miR-181a/b and 200b/c) in GBM 6).
Huang et al., showed that miR-181a and it targets ANGPT2 and LAMC1 might be predictors of prognosis in GBM patients 7).
CASC2 could inhibit the miR-181a expression by direct targeting in TMZ-resistant glioma cells. CASC2 up-regulated PTEN protein and down-regulated p-AKT protein through regulating miR-181a, and the effect of CASC2 on PTEN and p-AKT could be partially restored by miR-181a. With TMZ-resistant glioma tissues, miR-181a was up-regulated while PTEN was down-regulated. Taken together, these observations suggest CASC2 up-regulates PTEN through direct inhibiting miR-181a and plays an important role in glioma sensitivity to TMZ and may serve as a potential target for cancer diagnosis and treatment 8).
High Notch2 expression together with low miR-181a expression was correlated with a shorter median overall survival for GBM patients. Together, these data show that miR-181a may play an essential role in GSC formation and GBM progression by targeting Notch2, suggesting that Notch2 and miR-181a have potential prognostic value as tumor biomarkers in GBM patients 9).
A transient increase in miR-181a expression was observed after conditioned fear conditioning (CFC) and object location task (OLT) training. Selective overexpression or inhibition of miR-181a in the dorsal hippocampus (DH) via the injection of a miR-181a agomir or antagomir enhanced or impaired the CFC- and OLT-dependent memory formation, respectively. Using bioinformatics and luciferase assays, we identified PRKAA1 as a potential target gene of miR-181a. After CFC or OLT training, the expression and activity of PRKAA1 decreased as miR-181a expression increased and was effectively blocked by the miR-181a antagomir. Moreover, microinjection of the PRKAA1 agonist AICAR or inhibitor compound C in the DH reversed the roles of the miR-181a agomir or antagomir in CFC- and OLT-dependent memory formation. In conclusion, this work provides novel evidence describing the role and mechanism of miR-181a in hippocampus-dependent memory formation, which sheds light on the potential regulation of cognition and future treatments for cognitive disorders 10).
miR 181a plays critical roles in multiple cancers; however, its precise mechanisms in glioma have not been well clarified. The goal of a study of Wang et al., from the Harbin Medical University, Harbin, China, was to evaluate the interaction between Kaiso and miR-181a in glioma.
Quantitative real-time PCR (qRT-PCR) was performed to detect the levels of Kaiso and miR-181a in glioma tissues and cell lines. Cell proliferation, invasion, and the Epithelial-mesenchymal-transition (EMT) were evaluated to analyze the biological functions of miR-181a and Kaiso in glioma cells. The mRNA and protein levels of Kaiso were measured by qRT-PCR and western blotting, respectively. Meanwhile, luciferase assays were performed to validate Kaiso as a miR-181a target in glioma cells.
They found that the level of miR-181a was the lowest among miR-181a-d in glioma tissues and cell lines, and the low level of miR-181a was closely associated with the increased expression of Kaiso in glioma tissues. Moreover, transfection of miR-181a significantly inhibited the proliferation, invasion, and EMT of glioma cells, whereas knockdown of miR-181a had the opposite effect. Bioinformatics analysis predicted that Kaiso was a potential target gene of miR-181a, and the luciferase reporter assay demonstrated that miR-181a could directly target Kaiso. In addition, Kaiso silencing had similar effects as miR-181a overexpression in glioma cells, whereas overexpression of Kaiso in glioma cells partially reversed the inhibitory effects of the miR-181a mimic.
miR-181a inhibited the proliferation, invasion, and EMT of glioma cells by directly targeting and downregulating Kaiso expression 11).