title: Linc-ROR induces epithelial-mesenchymal transition and contributes to drug resistance and invasion of breast cancer cells.
abstract: We aimed to investigate the role of large intergenic noncoding RNA regulator of reprogramming (linc-ROR) in the chemotherapy resistance of human breast cancer (BC) cells and its mechanism. A total of 142 patients diagnosed with BC in the First Affiliated Hospital, Zhejiang University between January 2012 and January 2014 were enrolled in our study. The BC tissues and the adjacent normal tissues (5 cm away from tumor tissue) of the enrolled patients were selected, and human BC cell lines (MCF10A, SK-BR-3, MCF-7, Bcap-37, MDA-MB-231, and T47D) were also selected. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay, and Transwell were applied in our study. Expression level of linc-ROR messenger RNA (mRNA) in BC tissues was clearly higher than that in adjacent normal tissues, and significant difference was found between expression level of linc-ROR mRNA and lymph node metastasis (all P < 0.05). Linc-ROR was highly expressed in others BC cell lines compared with that in immortalized mammary epithelial cells (MECs) MCF10A (both P < 0.05), while MDA-MB231 cell presented the higher expression (P < 0.001). Under different concentrations of 5-FU and paclitaxel in MDA-MB231 cell, E-cadherin mRNA and protein expressions increased gradually with the increase of concentrations, and Vimentin and N-cadherin mRNA and protein expressions decreased gradually with the decrease of concentrations (all P < 0.05). Compared with shCtrl group, MDA-MB231 cell in shROR group presented higher sensibility of 5-FU and paclitaxel with increased E-cadherin expression, decreased Vimentin and N-cadherin expression and invasion ability (all P < 0.05). Compared with vector cell, overexpressed linc-ROR cell presented decreased sensibility of 5-FU and paclitaxel with decreased E-cadherin expression, increased Vimentin, N-cadherin expression, and invasion ability (all P < 0.05). Our study demonstrated that linc-ROR is an important marker for multidrug resistance of BC, and its up-regulation is important for chemotherapy tolerance and invasion of BC.
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University, No.79 Qingchun Road, Hangzhou, 310000, People's Republic of China.
authors.forename: Yao-Min
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University, No.79 Qingchun Road, Hangzhou, 310000, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University, No.79 Qingchun Road, Hangzhou, 310000, People's Republic of China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Wei
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University, No.79 Qingchun Road, Hangzhou, 310000, People's Republic of China.
authors.forename: Ke-Zhen
authors.initials: KZ
authors.lastname: Lv
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital, Zhejiang University, No.79 Qingchun Road, Hangzhou, 310000, People's Republic of China. fupeifen_perry@163.com.
authors.forename: Peifen
authors.initials: P
authors.lastname: Fu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C000588825:Linc-RNA-RoR, human; D062085:RNA, Long Noncoding
keywords: 5-Fluorouracil; Breast cancer; Epithelial-mesenchymal transition; Invasion; Large intergenic noncoding RNA regulator of reprogramming; MDA-MB231 cell; Paclitaxel