MicroRNA Expression Profile of Neural Progenitor-Like Cells Derived from Rat Bone Marrow Mesenchymal Stem Cells under the Influence of IGF-1, bFGF and EGF.
Insulin-like growth factor 1 (IGF-1) enhances cellular proliferation and reduces apoptosis during the early differentiation of bone marrow derived mesenchymal stem cells (BMSCs) into neural progenitor-like cells (NPCs) in the presence of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). BMSCs were differentiated in three groups of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1, and (C) without growth factor. To unravel the molecular mechanisms of the NPCs derivation, microarray analysis using GeneChip miRNA arrays was performed. The profiles were compared among the groups. Annotated microRNA fingerprints (GSE60060) delineated 46 microRNAs temporally up-regulated or down-regulated compared to group C. The expressions of selected microRNAs were validated by real-time PCR. Among the 46 microRNAs, 30 were consistently expressed for minimum of two consecutive time intervals. In Group B, only miR-496 was up-regulated and 12 microRNAs, including the let-7 family, miR-1224, miR-125a-3p, miR-214, miR-22, miR-320, miR-708, and miR-93, were down-regulated. Bioinformatics analysis reveals that some of these microRNAs (miR-22, miR-214, miR-125a-3p, miR-320 and let-7 family) are associated with reduction of apoptosis. Here, we summarize the roles of key microRNAs associated with IGF-1 in the differentiation of BMSCs into NPCs. These findings may provide clues to further our understanding of the mechanisms and roles of microRNAs as key regulators of BMSC-derived NPC maintenance.
Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Jalan Raja Perempuan Zainab II, 16150 Kubang Kerian, Kota Bharu, Kelantan, Malaysia. teejonghuat@gmail.com.|Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Jalan Raja Perempuan Zainab II, 16150 Kubang Kerian, Kota Bharu, Kelantan, Malaysia. teejonghuat@gmail.com.
Tee Jong
TJ
Huat
Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Jalan Raja Perempuan Zainab II, 16150 Kubang Kerian, Kota Bharu, Kelantan, Malaysia. amkhan@sharjah.ac.ae.|Department of Applied Biology, College of Sciences, University of Sharjah, Emirates of Sharjah, P.O. Box 27272, United Arab Emirates. amkhan@sharjah.ac.ae.|Sharjah Institute for Medical Research, University of Sharjah, Emirates of Sharjah, P.O. Box 27272, United Arab Emirates. amkhan@sharjah.ac.ae.
Amir Ali
AA
Khan
Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Jalan Raja Perempuan Zainab II, 16150 Kubang Kerian, Kota Bharu, Kelantan, Malaysia. brainsciences@gmail.com.|Director, Center for Neuroscience Services and Research, Universiti Sains Malaysia, Jalan Raja Perempuan Zainab II, 16150 Kubang Kerian, Kota Bharu, Kelantan, Malaysia. brainsciences@gmail.com.|Jabatan Neurosains, Hospital Universiti Sains Malaysia, Jalan Raja Perempuan Zainab II, 16150 Kubang Kerian, Kota Bharu, Kelantan, Malaysia. brainsciences@gmail.com.
Jafri Malin
JM
Abdullah
Department of Medical Microbiology, School of Medical Sciences, Universiti Sains Malaysia, Jalan Raja Perempuan Zainab II, 16150 Kubang Kerian, Kota Bharu, Kelantan, Malaysia. fauziahmi@usm.my.
Fauziah Mohamad
FM
Idris
Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Jalan Raja Perempuan Zainab II, 16150 Kubang Kerian, Kota Bharu, Kelantan, Malaysia. hasnan@usm.my.
Hasnan
H
Jaafar
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016000:Cluster Analysis; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D020869:Gene Expression Profiling; D063990:Gene Ontology; D053263:Gene Regulatory Networks / Q000187:drug effects; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology*; D020411:Oligonucleotide Array Sequence Analysis; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D012984:Software; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D035683:MicroRNAs; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I