title: MiR-145 regulates cancer stem-like properties and epithelial-to-mesenchymal transition in lung adenocarcinoma-initiating cells.
abstract: MicroRNA-145 (MiR-145) is an important regulator of tumorigenesis. Our previous work indicated that miR-145 reduced the proliferation and invasion as well as the tumorosphere growth capacity in lung adenocarcinoma cells. However, the underlying molecular mechanisms remain elusive. Here, we reported that the expression level of miR-145 was downregulated in lung adenocarcinoma tissues and negatively correlated with the expression level of Oct4. MiR-145 inhibited the proliferation of lung cancer-initiating cells (LCICs), partially by regulating Oct4 expression. Furthermore, we found that miR-145 exerted repressive effect on cancer stem cell properties and inhibited epithelial-mesenchymal transition (EMT) in vitro, also partially by regulating Oct4. Finally, we confirmed the repressive effect of miR-145 on cancer stem cell properties and EMT in vivo. Taken together, these evidences suggest that miR-145 serves as a tumor suppressor which downregulates LCICs' cancer stem cell properties and EMT process by targeting Oct4, leading to the inhibition of tumor growth and metastasis.
authors.affiliation: Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing, 210009, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Hu
authors.forename: Mantang
authors.initials: M
authors.lastname: Qiu
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Rong
authors.initials: R
authors.lastname: Yin
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics*; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human