TY - JOUR
T1 - Impact of miRNA-mRNA Profiling and Their Correlation on Medulloblastoma Tumorigenesis
AU - Kumar, Vinod
AU - Kumar, Virender
AU - Chaudhary, Amit Kumar
AU - Coulter, Donald W.
AU - McGuire, Timothy
AU - Mahato, Ram I.
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2018/9/7
Y1 - 2018/9/7
N2 - Medulloblastoma (MB) is a clinically challenging, childhood brain tumor with a diverse genetic makeup and differential miRNA profile. Aiming to identify deregulated miRNAs in MB, the miRNA expression profile of human MB samples was compared to that of normal cerebellar tissues. As a result, 8 upregulated and 64 downregulated miRNAs were identified in MB samples. Although various algorithms have been developed to predict the interaction between miRNA-mRNA pairs, the complexity and fidelity of miRNA-mRNA remain a concern. Therefore, to identify the signatures of miRNA-mRNA interactions essential for MB pathogenesis, miRNA profiling, RNA sequencing, and ingenuity pathway analysis (IPA) were performed in the same primary human MB samples. Further, when miR-217 was inhibited, a significant upregulation of predicted target genes SIRT1, ROBO1, FOXO3, and SMAD7 in HDMB03 cells was observed, confirming the validity of our approach. Functional analysis revealed that the inhibition of miR-217 in HDMB03 cells suppresses colony formation, migration, invasion, promoted apoptosis, and arrested cell population in S phase, indicating that manipulation of miR-217 may have a therapeutic potential for MB patients. Therefore, our study provides an essential platform for future investigations of specific miRNAs responsible for MB pathogenesis.
AB - Medulloblastoma (MB) is a clinically challenging, childhood brain tumor with a diverse genetic makeup and differential miRNA profile. Aiming to identify deregulated miRNAs in MB, the miRNA expression profile of human MB samples was compared to that of normal cerebellar tissues. As a result, 8 upregulated and 64 downregulated miRNAs were identified in MB samples. Although various algorithms have been developed to predict the interaction between miRNA-mRNA pairs, the complexity and fidelity of miRNA-mRNA remain a concern. Therefore, to identify the signatures of miRNA-mRNA interactions essential for MB pathogenesis, miRNA profiling, RNA sequencing, and ingenuity pathway analysis (IPA) were performed in the same primary human MB samples. Further, when miR-217 was inhibited, a significant upregulation of predicted target genes SIRT1, ROBO1, FOXO3, and SMAD7 in HDMB03 cells was observed, confirming the validity of our approach. Functional analysis revealed that the inhibition of miR-217 in HDMB03 cells suppresses colony formation, migration, invasion, promoted apoptosis, and arrested cell population in S phase, indicating that manipulation of miR-217 may have a therapeutic potential for MB patients. Therefore, our study provides an essential platform for future investigations of specific miRNAs responsible for MB pathogenesis.
KW - RNA-seq
KW - medulloblastoma
KW - miR-217
KW - miRNA profiling
KW - miRNA-mRNA correlation
UR - http://www.scopus.com/inward/record.url?scp=85049791976&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049791976&partnerID=8YFLogxK
U2 - 10.1016/j.omtn.2018.06.004
DO - 10.1016/j.omtn.2018.06.004
M3 - Article
C2 - 30195786
AN - SCOPUS:85049791976
SN - 2162-2531
VL - 12
SP - 490
EP - 503
JO - Molecular Therapy Nucleic Acids
JF - Molecular Therapy Nucleic Acids
ER -