title: miR-19a promotes colitis-associated colorectal cancer by regulating tumor necrosis factor alpha-induced protein 3-NF-κB feedback loops.
abstract: Chronic inflammation is believed to have a crucial role in colon cancer development. MicroRNA (miRNA) deregulation is common in human colorectal cancers, but little is known regarding whether miRNA drives tumor progression by regulating inflammation. Here, we showed that miR-19a can promote colitis and colitis-associated colon cancer (CAC) development using a CAC mouse model and an acute colitis mouse model. Tumor necrosis factor-α (TNF-α) stimulation can increase miR-19a expression, and upregulated miR-19a can in turn activate nuclear factor (NF)-κB signaling and TNF-α production by targeting TNF alpha-induced protein 3 (TNFAIP3). miR-19a inhibition can also alleviate CAC in vivo. Moreover, the regulatory effects of miR-19a on TNFAIP3 and NF-κB signaling were confirmed using tumor samples from patients with colon cancer. These new findings demonstrate that miR-19a has a direct role in upregulating NF-κB signaling and that miR-19a has roles in inflammation and CAC.
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, China.|Department of Molecular and Cellular Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.affiliation: General Surgery, Jinling Hospital, Medical School, Nanjing University, Nanjing, China.
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Xu
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
authors.forename: J
authors.initials: J
authors.lastname: Ren
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, China.
authors.forename: S
authors.initials: S
authors.lastname: Shen
authors.affiliation: General Surgery, Jinling Hospital, Medical School, Nanjing University, Nanjing, China.
authors.forename: C
authors.initials: C
authors.lastname: Fan
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D003092:Colitis / Q000139:chemically induced / Q000150:complications*; D015179:Colorectal Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3