title: Identification of carcinogenic potential-associated molecular mechanisms in CD133(+) A549 cells based on microRNA profiles.
abstract: This study aimed to identify carcinogenic potential-related molecular mechanisms in cancer stem cells (CSCs) in lung cancer. CD133(+) and CD133(-) subpopulations were sorted from A549 cells using magnetic-activated cell sorting. The abilities to form sphere and clone, proliferate, migrate, and invade were compared between CD133(+) and CD133(-) cells, as well as drug sensitivity. Thereafter, microRNA (miRNA) profiles were performed to identify differentially expressed miRNAs between CD133(+) and CD133(-) subpopulation. Following, bioinformatic methods were used to predict target genes for differentially expressed miRNAs and perform enrichment analysis. Furthermore, the mammalian target of rapamycin (mTOR) signaling pathways and CSC property-associated signaling pathways were explored and visualized in regulatory network among competitive endogenous RNA (ceRNA), miRNA, and target gene. CD133(+) subpopulation showed greater oncogenic potential than CD133(-) subpopulation. In all, 14 differentially expressed miRNAs were obtained and enriched in 119 pathways, including five upregulated (hsa-miR-23b-3p, -23a-3p, -15b-5p, -24-3p, and -4734) and nine downregulated (hsa-miR-1246, -30b-5p, -5096, -6510-5p, has-miR-7110-5p, -7641, -3197, -7108-5p, and -6791-5p). For mTOR signaling pathway, eight differential miRNAs (hsa-miR-23b-3p, -23a-3p, -15b-5p, -24-3p, -4734, -1246, -7641, and -3197) and 39 target genes (e.g., AKT1, AKT2, PIK3CB, PIK3CG, PIK3R1, PIK3CA, and PIK3CD) were involved, as well as some ceRNAs. Besides, for CSC property-related signaling pathways, six miRNAs (hsa-miR-1246, -15b-5p, -30b-5p, -3197, -4734, and -7110-5p) were dramatically enriched in Hedgehog, Notch, and Wnt signaling pathways via regulating 108 target genes (e.g., DVL1, DVL3, WNT3A, and WNT5A). The mTOR and CSC property-associated signaling pathways may be important oncogenic molecular mechanisms in CD133(+) A549 cells.
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, People's Republic of China. cqyong117@163.com.|Department of Respiratory Disease, The 117th Hospital of PLA, Hangzhou, 310013, Zhejiang Province, People's Republic of China. cqyong117@163.com.
authors.forename: Qing-Yong
authors.initials: QY
authors.lastname: Chen
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Hangzhou, 310013, Zhejiang Province, People's Republic of China.
authors.forename: De-Min
authors.initials: DM
authors.lastname: Jiao
authors.affiliation: Department of Oncology, The 117th Hospital of PLA, Hangzhou, 310013, Zhejiang Province, People's Republic of China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Hangzhou, 310013, Zhejiang Province, People's Republic of China.
authors.forename: Huizhen
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Hangzhou, 310013, Zhejiang Province, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Hangzhou, 310013, Zhejiang Province, People's Republic of China.
authors.forename: Xiali
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Hangzhou, 310013, Zhejiang Province, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Oncology, The 117th Hospital of PLA, Hangzhou, 310013, Zhejiang Province, People's Republic of China. yanli117117@sina.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
mesh_terms: D000072283:A549 Cells; D000071916:AC133 Antigen / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000737:chemistry; D063646:Carcinogenesis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002469:Cell Separation; D019295:Computational Biology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism; D014411:Neoplastic Stem Cells; D015398:Signal Transduction
chemical_list: D000071916:AC133 Antigen; D000970:Antineoplastic Agents; D035683:MicroRNAs
keywords: Bioinformatic methods; CD133; Cancer stem cell; MicroRNA profile; Non-small cell lung cancer; mTOR