title: miR-15b inhibits cancer-initiating cell phenotypes and chemoresistance of cisplatin by targeting TRIM14 in oral tongue squamous cell cancer.
abstract: Oral tongue squamous cell carcinoma (TSCC) is one of the most lethal cancers within the oral cavity and its prognosis remains dismal due to the paucity of effective therapeutic targets. The formation of cancer-initiating cells (CICs) and epithelial-mesenchymal transition (EMT) are pivotal events involved in the dismal prognosis. They have been shown to be related to the resistance to cisplatin treatment. In the present study, we showed that TRIM14 induced formation of cancer-initiating cells and EMT in TSCC SCC25 cells. Its overexpression promoted cisplatin resistance in the SCC25 cells. We found that overexpression of miR-15b suppressed TRIM14 and inhibited CIC phenotypes in the SCC25 cells. Moreover, overexpression of miR-15b promoted mesenchymal-epithelial transition (MET) in the SCC25 cells and sensitized cisplatin-resistant SCC25 (SCC25-res) cells to cisplatin. Thus, we conclude that miR-15b inhibited cancer stem cell phenotypes and its restoration reversed the chemoresistance of cisplatin by targeting TRIM14 in TSCC. Elucidating the molecular mechanism of EMT and cancer stem cells in TSCC may further aid in the understanding of the pathogenesis and progression of the disease, and offer novel targets for the discovery of new drugs.
authors.affiliation: Department of Prosthodontics, School of Stomatology, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Xijun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Periodontology, School of Stomatology, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Surgery, University of California Davis, Sacaramento, CA 95817, USA.
authors.forename: Banjamin
authors.initials: B
authors.lastname: Yao
authors.affiliation: Department of Surgery, University of California Davis, Sacaramento, CA 95817, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Helms
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs / Q000235:genetics*; D010641:Phenotype; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000070584:Tripartite Motif Proteins
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C505361:MIRN15 microRNA, human; D035683:MicroRNAs; C481145:TRIM14 protein, human; D000070584:Tripartite Motif Proteins; D002945:Cisplatin