title: microRNA-520a-3p inhibits proliferation and cancer stem cell phenotype by targeting HOXD8 in non-small cell lung cancer.
abstract: Formation of cancer stem cells (CSCs) and increased cells proliferation are involved in tumorigenesis, tumour recurrence and therapy resistance and microRNA is essential for the development of the biological traits of CSCs and the increased cells proliferation. Studying molecular mechanism of tumorigenesis, tumour recurrence and therapy resistance of lung cancer will help us to further understand the pathogenesis and progression of the disease and offer new targets for effective therapies. In the present study, we found that miR-520a-3p expression is downregulated in NSCLC (non-small cell lung cancer) and SCLC (small cell lung cancer). miR-520a-3p can inhibit proliferation and cancer stem cell phenotype in NSCLC and SCLC cells. Overexpressing miR-520a-3p can degrade HOXD8 mRNA in NSCLC cells, but its overexpression cannot suppress HOXD8 in SCLC cells. HOXD8 protein is upregulated in NSCLC tissues and its overexpression can promote proliferation, formation of cancer stem cells, migration and invasion in NSCLC cells. MET amplification plays a pivotal role in gefitinib resistance in lung cancer. We found that miR-520a-3p can downregulate MET protein expression and HOXD8 can upregulate MET protein expression. Thus, we concluded that microRNA-520a-3p inhibits proliferation and cancer stem cell phenotype by targeting HOXD8 in NSCLC cells and restoration of microRNA-520a-3p might be a therapeutic strategy to reverse gefitinib resistance.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Miao
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Ni
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Oncology Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Oncology Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Oncology Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000072283:A549 Cells; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010641:Phenotype; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D000093542:Gemcitabine
chemical_list: D020413:3' Untranslated Regions; D000964:Antimetabolites, Antineoplastic; D018398:Homeodomain Proteins; C575048:MIRN520 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; D003841:Deoxycytidine; C075279:HOXD8 protein, human; D000093542:Gemcitabine