title: Let-7a elevates p21(WAF1) levels by targeting of NIRF and suppresses the growth of A549 lung cancer cells.
abstract: Down-regulation of let-7 microRNA (miRNA) is a key event in lung cancer. Despite recent advances in survival signaling, the roles of let-7 in the context of lung cancer are not fully clear. In this study, we showed that let-7a, a member of let-7 family, negatively regulated the expression of NIRF through NIRF 3' UTR. We also showed that NIRF was required for the let-7a-mediated elevation of p21(WAF1). These findings suggest that growth-inhibitory effect of let-7a on the A549 cells in vitro and in vivo may be explained in part by le-7a-induced suppression of NIRF and elevation of p21(WAF1). This work reveals a novel regulatory mechanism for let-7a in the control of cellular proliferation and lung carcinogenesis.
authors.affiliation: Department of Cell Biology and Medical Genetics, Chongqing Medical University, No. 1, Medical College Road, Chongqing 400016, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: He
authors.forename: Changzhu
authors.initials: C
authors.lastname: Duan
authors.forename: Junxia
authors.initials: J
authors.lastname: Chen
authors.forename: Xi
authors.initials: X
authors.lastname: Ou-Yang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Chunlei
authors.initials: C
authors.lastname: Li
authors.forename: Huimin
authors.initials: H
authors.lastname: Peng
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D019295:Computational Biology; D017124:Conserved Sequence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; C465619:UHRF2 protein, human; D044767:Ubiquitin-Protein Ligases