Knockdown of ubiquitin-conjugating enzyme E2C/UbcH10 expression by RNA interference inhibits glioma cell proliferation and enhances cell apoptosis in vitro

Abstract PAI-1 plays significant roles in cancer occurrence, relapse and multidrug resistance and is highly expressed in tumours. ACT001, which is currently in phase I clinical trials for the treatment of glioblastoma (GBM). However, the detailed molecular mechanism of ACT001 is still unclear. In this study, we investigated the effects of ACT001 on glioma cell proliferation and clarified its mechanism. We discovered that PAI-1 was the direct target of ACT001 by a cellular thermal shift assay. Then, the interaction between ACT001 and PAI-1 was verified by Biacore assays, thermal stability assays and ACT001 probe assays. Furthermore, from the proteomic analysis, we found that ACT001 directly binds PAI-1 to inhibit the PI3K/AKT pathway, which induces the inhibition of glioma cell proliferation, invasion and migration. Moreover, the combination of ACT001 and cisplatin showed a synergistic effect on the inhibition of glioma in vitro and in vivo. In conclusion, our findings demonstrate that PAI-1 is a new target of ACT001, the inhibition of PAI-1 induces glioma inhibition, and ACT001 has a synergistic effect with cisplatin through the inhibition of the PAI-1/PI3K/AKT pathway.

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miR-103/miR-195/miR-15b Regulate SALL4 and Inhibit Proliferation and Migration in Glioma

Molecules ◽

10.3390/molecules23112938 ◽

2018 ◽

Vol 23 (11) ◽

pp. 2938 ◽

Cited By ~ 9

Author(s):

Li-Ping Chen ◽

Na-Na Zhang ◽

Xue-Qing Ren ◽

Jie He ◽

Yu Li

Keyword(s):

Cell Proliferation ◽

Cell Apoptosis ◽

Glioma Cell ◽

Inverse Correlation ◽

Primary Brain Tumor ◽

Migration And Invasion ◽

Glioma Cell Proliferation ◽

The Common ◽

Direct Target ◽

And Migration

Glioma is the common highly malignant primary brain tumor. However, the molecular pathways that result in the pathogenesis of glioma remain elusive. In this study, we found that microRNA-103 (miR-103), microRNA-195 (miR-195), or microRNA-15b (miR-15b), which all have the same 5′ “seed” miRNA portion and share common binding sites in the SALL4 3′-untranslated region (UTR), were downregulated in glioma tissues and cell lines. These miRNAs suppressed glioma cell proliferation, migration, and invasion, induced cell apoptosis, and decreased the level of the SALL4 protein, but not that of SALL4 mRNA, which was identified as a direct target of all three miRNAs. The caspase-3/7 activity expression in U251 cells overexpressing these miRNAs was rescued during SALL4 upregulation. An obvious inverse correlation was observed between SALL4 and miR-103 or miR-195 expression levels in clinical glioma samples. Moreover, enforced expression of SALL4 stimulated cell proliferation, migration, and invasion. In conclusion, these data suggest that miR-103, miR-195, and miR-15b post-transcriptionally downregulated the expression of SALL4 and suppressed glioma cell growth, migration, and invasion, and increased cell apoptosis. These results provide a potential therapeutic target that may downregulate SALL4 in glioma.

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