Linc-ROR induces epithelial-mesenchymal transition and contributes to drug resistance and invasion of breast cancer cells.

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.

Duodenal gastrointestinal stromal tumor: clinical, pathologic, immunohistochemical characteristics, and surgical prognosis.

OBJECTIVE: Gastrointestinal stromal tumors (GISTs) occur rarely in the duodenum. The characteristics of duodenal GIST have not been well clarified. The aim of this study is to clarify the characteristics and surgical prognosis of patients with primary duodenal GIST. METHODS: Data of patients with surgically treated primary duodenal GIST were retrospectively analyzed. Immunohistochemical expressions of p53, p16, and Ki-67 were evaluated to explain the prognosis. RESULTS: Compared with gastric or small intestinal GISTs in historical studies, duodenal GISTs had a relatively smaller size, lower mitotic count, lower Ki-67 LI, lower p16 loss, and similar p53 expression. The 1- and 3-year recurrence-free survival rates of patients with complete resection were 100 and 95.2%. CONCLUSION: Patients with completely resected primary duodenal GIST seem to have a more favorable prognosis. This may be related to the different expressions of some immunohistological makers compared with GISTs of other locations.

Large intergenic non-coding RNA-ROR reverses gemcitabine-induced autophagy and apoptosis in breast cancer cells.

The purpose of this study was to elucidate the potential role of long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) in gemcitabine (Gem)-induced autophagy and apoptosis in breast cancer cells. MDA-MB-231 cells were treated with short hairpin RNA (shRNA) to knockdown Linc-ROR expression in the presence of Gem. Gem treatment alone decreased cell survival and increased both apoptosis and autophagy. Gem treatment also increased the expression of LC3-II, Beclin 1, NOTCH1 and Bcl-2, but decreased expression of p62 and p53. Untreated MDA-MB-231 cell lines strongly expressed linc-ROR, but linc-ROR knockdown decreased cell viability and expression of p62 and p53 while increasing apoptosis. Linc-ROR knockdown also increased LC3-II/ß-actin, Beclin 1, NOTCH1, and Bcl-2 expression, as well as the number of autophagic vesicles in MDA-MB-231 cells. Linc-ROR negatively regulated miR-34a expression by inhibiting histone H3 acetylation in the miR-34a promoter. We conclude that linc-ROR suppresses Gem-induced autophagy and apoptosis in breast cancer cells by silencing miR-34a expression.