title: Regulation of miR-34 Family in Neuronal Development.
abstract: Differentiation of neural stem cells (NSC's) to mature and functional neurons requires coordinated expression of mRNA, microRNAs (miRNAs) and regulatory proteins. Our earlier unbiased miRNA profiling studies have identified miR-200, miR-34 and miR-221/222 as maximally up-regulated miRNA families in differentiating PC12 cells and demonstrated the capability of miR-200 family in inducing neuronal differentiation (J. Neurochem, 2015, 133, 640-652). In present study, we have investigated role of miR-34 family in neuronal differentiation and identified P53 as mediator of nerve growth factor (NGF) induced miR-34a expression in differentiating PC12 cells. Our studies have shown that NGF induced miR-34a, arrests proliferating PC12 cells to G1 phase, which is pre-requisite for neuronal differentiation. Our studies have also shown that increased expression of miR-34a controls the P53 level in differentiated PC12 cells in feedback inhibition manner, which probably prevents differentiated cells from P53 induced apoptosis. Expression profiling of miR-34 family in different neuronal, non-neuronal and developing cells have identified differentiated and aged brain cells as richest source of miR-34, which also indicates that higher expression of miR-34 family helps in maintaining the mature neurons in non-proliferative stage. In conclusion, our studies have shown that miR-34 is brain enriched miRNA family, which up-regulates with neuronal maturation and brain ageing and co-operative regulation of P53 and miR-34a helps in neuronal differentiation by arresting cells in G1 phase.
authors.affiliation: Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR- Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, 226001, India.|Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, India.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Jauhari
authors.affiliation: Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR- Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, 226001, India.|Department of Biochemistry, School of Dental Sciences, Babu Banarasi Das University, Lucknow, India.
authors.forename: Tanisha
authors.initials: T
authors.lastname: Singh
authors.affiliation: Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR- Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, 226001, India.|Department of Biochemistry, School of Dental Sciences, Babu Banarasi Das University, Lucknow, India.
authors.forename: Parul
authors.initials: P
authors.lastname: Singh
authors.affiliation: Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR- Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, 226001, India.
authors.forename: Devendra
authors.initials: D
authors.lastname: Parmar
authors.affiliation: Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR- Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, 226001, India. sanjay@iitr.res.in.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Yadav
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs
keywords: Cell cycle arrest; Neuronal differentiation; P53; PC12 cells; miR-34; microRNAs