title: MicroRNA-9 regulates neural apoptosis in methylmalonic acidemia via targeting BCL2L11.
abstract: Methylmalonic acidemia (MMA) is an autosomal-recessive inborn metabolic disorder that results from a deficiency in methylmalonyl-coenzyme A mutase or its cofactor, adenosylcobalamin. Currently, neurological manifestations in MMA are thought to be associated with neural apoptosis. BCL2L11, which is a proapoptotic Bcl-2 family member, is resident in the outer mitochondrial membrane, where this protein acts as a central regulator of the intrinsic apoptotic cascade and mediates excitotoxic apoptosis. MicroRNAs (miRNAs) are a class of non-coding RNAs that function as endogenous triggers of the RNA interference pathway. Currently, little is known regarding the role of miRNA in MMA. In our previous study, we preliminarily found that the expression of miR-9 was significantly down-regulated in MMA patient plasma and sensitively changed after VitB12 treatment, which may act as a potential "competitor" of gas chromatography-mass spectrometry for the diagnosis of MMA. In the present study, we first confirmed that miR-9 inhibited BCL2L11 expression by directly targeting its 3'-untranslated region, and the up-regulation of miR-9 reduced neural apoptosis induced by methylmalonate via targeting BCL2L11. Taken together, our results suggested that miR-9 might act as a monitor of changes in MMA and might provide new insights into a therapeutic entry point for treating MMA.
authors.affiliation: Department of Neurology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.affiliation: Department of Neurology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Duan
authors.affiliation: Department of Neurology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Huili
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Neurology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Guan
authors.affiliation: Department of Neurology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Neurology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Junfang
authors.initials: J
authors.lastname: Teng
authors.affiliation: Department of Neurology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China. Electronic address: jiayanjie1971@aliyun.com.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Jia
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D002540:Cerebral Cortex / Q000166:cytology; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008764:Methylmalonic Acid / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; C541874:MIRN92 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D008764:Methylmalonic Acid
keywords: Apoptosis; BCL2L11; Methylmalonic acidemia; MicroRNA-9