title: Synaptic acetylcholinesterase targeted by microRNA-212 functions as a tumor suppressor in non-small cell lung cancer.
abstract: Acetylcholinesterase expression is modulated in various types of tumor, which suggests it is associated with tumor development; however, the mechanism of acetylcholinesterase gene regulation in tumors remains unclear. Here, we report that acetylcholinesterase is aberrantly expressed in non-small cell lung cancer and is an evolutionarily conserved functional target of miR-212. Acetylcholinesterase expression was negatively regulated by miR-212 in vitro and was inversely correlated with miR-212 expression in vivo. In addition, acetylcholinesterase levels were increased, and miR-212 levels decreased, in non-small cell lung cancer cells during cisplatin-induced apoptosis. We further determined that acetylcholinesterase acted as a pro-apoptotic gene in non-small cell lung cells; and attenuated the growth of xenografts in nude mice when upregulated. In contrast, elevated miR-212 levels preserved the protective effect of acetylcholinesterase silencing by RNA interference against cisplatin-induced apoptosis, whereas restoration of miR-212-resistant synaptic acetylcholinesterase expression inhibited the miR-212 anti-apoptotic function. The results demonstrated that miR-212 exerted an anti-apoptotic effect through direct repression of synaptic acetylcholinesterase expression in non-small cell lung cancer cells. Taken together, our study revealed that synaptic acetylcholinesterase may be a tumor suppressor and is modulated by miR-212 in non-small cell lung cancer.
authors: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Lu
authors: L
authors: Lu
authors: Xuejin
authors: X
authors: Zhang
authors: Bo
authors: B
authors: Zhang
authors: Jun
authors: J
authors: Wu
authors: Xuejun
authors: X
authors: Zhang
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D013569:Synapses / Q000187:drug effects / Q000201:enzymology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C551411:MIRN212 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; D000110:Acetylcholinesterase; D002945:Cisplatin
keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; AChE; AChE-E; AChE-R; AChE-S; Acetylcholinesterase; Apoptosis; CDDP; HCC; IHC; ISH; LNA; MMP; MTT; MiR-212; NSCLC; Non-small cell lung cancer; PARP; RNA interference; RNAi; TUNEL; TdT-mediated dUTP nick end labeling; Tumor suppressor; UTR; acetylcholinesterase; cisplatin; erythrocyte acetylcholinesterase; hepatocellular carcinoma; immunohistochemistry; in situ hybridization; locked nucleic acid; mitochondrial membrane permeability; non-small cell lung cancer; poly(ADP-ribose) polymerase; readthrough acetylcholinesterase; siRNA; small interfering RNA; synaptic acetylcholinesterase; untranslated region