title: MicroRNA-650 was a prognostic factor in human lung adenocarcinoma and confers the docetaxel chemoresistance of lung adenocarcinoma cells via regulating Bcl-2/Bax expression.
abstract: Increasing evidence shows that dysregulation of microRNAs (miRNAs) is involved in malignant transformation. We investigated the clinical significance of miR-650 and its involvement in chemoresistance to docetaxel. Our results showed that the relative expression level of miR-650 was significantly higher in LAD tissues than in corresponding nontumor tissues and high level of miR-650 expression was found to be significantly associated with high incidence of lymph node metastasis, advanced clinical stage and poor prognosis of LAD patients. Univariate and multivariate analyses indicated that high miR-650 expression was an independent prognostic factor for survival. Also, we found that the level of miR-650 in LAD tissues was correlated with the response of patients to docetaxel-based chemotherapy. Silencing of miR-650 could increase the in vitro sensitivity of docetaxel-resistant LAD cells to docetaxel, while upregulation of miR-650 decreased the sensitivity of parental LAD cells to docetaxel both in vitro and in vivo. Additionally, silencing of miR-650 could enhance the caspase-3-dependent apoptosis, which might be correlated with the decreased ratio of Bcl-2/Bax. Further researches suggested that inhibitor of growth 4 (ING4) was a direct target of miR-650. Downregulated or upregulated ING4 expression could partially rescue the effects of miR-650 inhibitor or mimics in docetaxel-resistant or parental LAD cells. Furthermore, we found that ING4 was upregulated in docetaxel-responding LAD tissues, and its expression was inversely correlated with miR-650. Thus, miR-650 is a novel prognostic marker in LAD and its expression is a potential indicator of chemosensitivity to docetaxel-based chemotherapy regimen.
authors.affiliation: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, PR China.
authors.forename: Jia-Yuan
authors.initials: JY
authors.lastname: Huang
authors.forename: Shi-Yun
authors.initials: SY
authors.lastname: Cui
authors.forename: Yi-Tian
authors.initials: YT
authors.lastname: Chen
authors.forename: Hai-Zhu
authors.initials: HZ
authors.lastname: Song
authors.forename: Gui-Chun
authors.initials: GC
authors.lastname: Huang
authors.forename: Bing
authors.initials: B
authors.lastname: Feng
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: De
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Long-Bang
authors.initials: LB
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D017931:DNA Primers; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D043823:Taxoids / Q000627:therapeutic use*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D017931:DNA Primers; C550124:MIRN650 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D043823:Taxoids; D051028:bcl-2-Associated X Protein; D000077143:Docetaxel