OBJECTIVETo identify novel lncRNAs involved in cerebellar neurogenesis using neuronal specific Nbs1-deficient (Nbs1(CNS-del)) mouse model.

METHODSMicroarray analysis was performed to identify differentially expressed lncRNAs between Nbs1(CNS-ctr) and Nbs1(CNS-del) mice. Expression profiles of lncRNA Gm15577 and coding gene Negr1 in mice, primary cerebellar culture and cell lines were measured using RT-qPCR. Subcellular fractionation was performed to determine the subcellular localization of Gm15577.

RESULTSGm15577 was specifically expressed in mice cerebellum in a developmentally regulated manner, which could be abolished upon Nbs1-deficiency. Gm15577 was located in the intronic region of Negr1 in a reversed orientation. Gm15577 modulated the RNA expression of Negr1, Shh and β-catenin. NEGR1 had a distinct expression pattern between normal and medulloblastoma patients.

CONCLUSIONGm15577 may modulate cerebellar granule cell proliferation and differentiation by targeting Negr1, and their dysfunctions or abnormal expression may be related to tumorigenesis of medulloblastoma.

Animals ; Cell Differentiation ; Cell Proliferation ; Cell Transformation, Neoplastic ; Cerebellar Neoplasms ; pathology ; Cerebellum ; cytology ; physiology ; Disease Models, Animal ; Humans ; Introns ; Medulloblastoma ; pathology ; Mice ; Mice, Knockout ; Neurogenesis ; Neurons ; physiology ; RNA, Long Noncoding ; metabolism

Objective: To investigate the role of Mic60 in cardiac aging. Methods: Wild-type and Mic60^{+ /-} male mice at age of 4-6 months (young group, n=6) and 18-20 months (aged group, n=9) were used. H&E and Masson staining of frozen and paraffin sections were subjected to morphologic evaluation of the cardiac tissue samples. SA-β-Gal staining was utilized to detect the activity of senescence-associated β-galactosidase. Western blot was performed to detect the expression of Mic60 and p21 in cardiac tissues. Results: Expression of Mic60 in mouse cardiac tissue increased in an age-dependent manner. Haploid insufficiency of Mic60 resulted in an increased left ventricular wall thickness [(1.32±0.09) mm vs.(1.12±0.09) mm, P<0.05], cardiomyocyte hypertrophy[(474.9±27.6) μm² vs.(358.8±48.7) μm², P<0.05] and interstitial fibrosis [ (38.24±7.58) ×10³μm² vs.(25.81±4.12)×10³μm^2, P<0.05], increased activity of SA-β-Gal (2.26±0.24 vs.0.25±0.05, P<0.01) and higher expression of p21 (P<0.01) in aged mouse cardiac tissue, but not in young mice. Conclusion Haploid insufficiency of Mic60 leads to cardiac hypertrophy, interstitial fibrosis, increased activity of SA-β-Gal and higher expression of p21 in aged cardiac tissue in mice, suggesting that Mic60 may prevent cardiac aging.