Abstract
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.
Highlights
Glioma is the common highly malignant primary brain tumor, and despite recent advances in the currently available therapeutic interventions, the median time of survival is less than 16 months after diagnosis [1]
Compared to normal brain tissues, the expression of miR-103, miR-195, and miR-15b was statistically significantly downregulated in tumor tissues (Figure 1A–C, p
We examined the expression of the three miRNAs in several glioma cell lines, including U251, U87, MO59K, and SHG44
Summary
Glioma is the common highly malignant primary brain tumor, and despite recent advances in the currently available therapeutic interventions, the median time of survival is less than 16 months after diagnosis [1]. SALL4, a zinc-finger transcription factor, is a member of the SALL gene family, and is located on chromosome 20. It was first cloned based on its sequence homology with Drosophila spalt [2,3]. Human SALL4 plays a pivotal role in maintaining the pluripotency and self-renewal characteristics of embryonic and hematopoietic stem cells [4,5]. We demonstrated that SALL4 is critical for gliomagenesis, and that the upregulation of miR-107 suppresses glioma cell growth through direct targeting of SALL4 [11]. Other groups have indicated that miRNA-98, miRNA-33b, and miRNA-219 play tumor-suppressive roles in cancer by targeting SALL4 [12,13,14,15]. The mechanisms controlling glioma cell proliferation, migration, and invasion through miRNAs targeting SALL4 remain relatively unknown
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