Genomic analyses reveal broad impact of miR-137 on genes associated with malignant transformation and neuronal differentiation in glioblastoma cells.
miR-137 plays critical roles in the nervous system and tumor development; an increase in its expression is required for neuronal differentiation while its reduction is implicated in gliomagenesis. To evaluate the potential of miR-137 in glioblastoma therapy, we conducted genome-wide target mapping in glioblastoma cells by measuring the level of association between PABP and mRNAs in cells transfected with miR-137 mimics vs. controls via RIPSeq. Impact on mRNA levels was also measured by RNASeq. By combining the results of both experimental approaches, 1468 genes were found to be negatively impacted by miR-137--among them, 595 (40%) contain miR-137 predicted sites. The most relevant targets include oncogenic proteins and key players in neurogenesis like c-KIT, YBX1, AKT2, CDC42, CDK6 and TGFβ2. Interestingly, we observed that several identified miR-137 targets are also predicted to be regulated by miR-124, miR-128 and miR-7, which are equally implicated in neuronal differentiation and gliomagenesis. We suggest that the concomitant increase of these four miRNAs in neuronal stem cells or their repression in tumor cells could produce a robust regulatory effect with major consequences to neuronal differentiation and tumorigenesis.
Authors
Saleh Tamim; Dat T Vo; Philip J Uren; Mei Qiao; Eckart Bindewald; Wojciech K Kasprzak; Bruce A Shapiro; Helder I Nakaya; Suzanne C Burns; Patricia R Araujo; Ichiro Nakano; Agnes J Radek; Scott Kuersten; Andrew D Smith; Luiz O F Penalva
External link
Publication Year
Publication Journal
Associeted Project
Integrative Biology
Lista de serviços
-
As antisense RNA gets intronic.As antisense RNA gets intronic.
-
Androgen responsive intronic non-coding RNAs.Androgen responsive intronic non-coding RNAs.
-
Conserved tissue expression signatures of intronic noncoding RNAs transcribed from human and mouse loci.Conserved tissue expression signatures of intronic noncoding RNAs transcribed from human and mouse loci.
-
The intronic long noncoding RNA ANRASSF1 recruits PRC2 to the RASSF1A promoter, reducing the expression of RASSF1A and increasing cell proliferation.The intronic long noncoding RNA ANRASSF1 recruits PRC2 to the RASSF1A promoter, reducing the expression of RASSF1A and increasing cell proliferation.
-
Antisense intronic non-coding RNA levels correlate to the degree of tumor differentiation in prostate cancer.Antisense intronic non-coding RNA levels correlate to the degree of tumor differentiation in prostate cancer.
-
Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon Leishmania infantum Infection.Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon Leishmania infantum Infection.
-
Long non-coding RNAs associated with infection and vaccine-induced immunityLong non-coding RNAs associated with infection and vaccine-induced immunity
-
Comparative transcriptomic analysis of long noncoding RNAs in Leishmania-infected human macrophagesComparative transcriptomic analysis of long noncoding RNAs in Leishmania-infected human macrophages