title: MicroRNA-432 functions as a tumor suppressor gene through targeting E2F3 and AXL in lung adenocarcinoma.
abstract: Abnormal proliferation and drug resistance are the hallmarks of lung adenocarcinoma (LAD). Dispite the advances in diagnosis and therapy, the 5-year survival remains low. Increasing studies regarding its pathological mechanism have been focused on microRNA (miRNA) due to its nodal regulatory properties. This study aims to characterize the expression of miR-432 in LAD and investigate its effects on the proliferation and sensitivity of lung cancer cells to cisplatin. Here, we report that downregulation of miR-432 in LAD tissues was correlated with a higher clinical stage (p = 0.03) and poor prognosis (p = 0.036). Additionally, miR-432 expression was negative correlated with high Ki67 labeling index (p = 0.016) in our cohorts. Functionally, over-expression of miR-432 inhibits cell proliferation through arresting cell cycle and sensitizes tumor cells to cisplatin. Mechanistically, miR-432 functions by directly targeting E2F3 and AXL, and they, in turn, mediate the regulation of miR-432 towards cell proliferation and cisplatin sensitivity. Importantly, miR-432 levels are negatively correlated with the levels of E2F3 and AXL in human LAD tissues. These results demonstrated that miR-432 functions as a tumor-suppressive miRNA and may represent a prognostic parameter and therapeutic target for LAD.
authors.affiliation: Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, China.|Department of Oncology, Qingdao Municipal Hospital, Qingdao, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Emergency Department, Qingdao Municipal Hospital, Qingdao, China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Kong
authors.affiliation: Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Chuantao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Linyi People's Hospital, Linyi, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Pathology, Linyi People's Hospital, Linyi, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Yang
authors.affiliation: Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China.
authors.forename: Guanhua
authors.initials: G
authors.lastname: Song
authors.affiliation: Department of Oncology, Qingdao Municipal Hospital, Qingdao, China.
authors.forename: Chengye
authors.initials: C
authors.lastname: Guo
authors.affiliation: Research Center for Medicinal Biotechnology, Key Laboratory for Rare and Uncommon Diseases of Shandong Province, Shandong Academy of Medical Sciences, Jinan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Yu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D050699:E2F3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D014408:Biomarkers, Tumor; D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; C582553:MIRN432 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase
keywords: AXL; E2F3; lung adenocarcinoma; miR-432