100885779

LINC-ROR

LncRNAs have critical roles in various biological processes ranging from embryonic development to human diseases, including cancer progression, although their detailed mechanistic functions remain illusive. The lncRNA linc-ROR has been shown to contribute to the maintenance of induced pluripotent stem cells and embryonic stem cells. In this study, we discovered that linc-ROR was upregulated in breast tumor samples, and ectopic overexpression of linc-ROR in immortalized human mammary epithelial cells induced an epithelial-to-mesenchymal transition (EMT) program. Moreover, we showed that linc-ROR enhanced breast cancer cell migration and invasion, which was accompanied by generation of stem cell properties. Contrarily, silencing of linc-ROR repressed breast tumor growth and lung metastasis in vivo. Mechanistically, our data revealed that linc-ROR was associated with miRNPs and functioned as a competing endogenous RNA to mi-205. Specifically, linc-ROR prevented the degradation of mir-205 target genes, including the EMT inducer ZEB2. Thus our results indicate that linc-ROR functions as an important regulator of EMT and can promote breast cancer progression and metastasis through regulation of miRNAs. Potentially, the findings of this study implicate the relevance of linc-ROR as a possible therapeutic target for aggressive and metastatic breast cancers.

Emerging evidence indicates that the dysregulation of long non-coding RNAs (lncRNAs) contributes to the development and progression of lung adenocarcinoma (LAD), however the underlying mechanism of action of lncRNAs remains unclear. It is well known that the effective treatment of cancers has been hindered by drug resistance in the clinical setting. epithelial-mesenchymal transition (EMT) has been recognized to be involved in acquiring drug resistance, cell migration and invasion properties in several types of cancer. Docetaxel-resistant LAD cells established previously in our lab present chemoresistant and mesenchymal features. Long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR), was first discovered in induced pluripotent stem cells (iPSCs) and was upregulated in docetaxel-resistant LAD cells. In this study, we tried to make clarification of lincRNA-related mechanisms underlying EMT followed by acquired resistance to chemotherapy in LAD. In order to hit the mark, we made use of multiple methods including microarray analysis, qRT-PCR, western blotting analysis, loss/gain-of-function analysis, luciferase assays, drug sensitivity assays, wound-healing assay and invasion assay. We found that decreased expression of linc-ROR effectively reversed EMT in docetaxel-resistant LAD cells and sensitized them to chemotherapy. The function of linc-ROR exerted in LAD cells depended on the sponging of miR-145, therefore, releasing the miR-145 target FSCN1, and thus contributing to the acquisition of chemoresistance and EMT phenotypes of docetaxel-resistant LAD cells. Our findings revealed that linc-ROR might act as potential therapeutic target to overcome chemotherapy resistance in LAD.

BACKGROUND: LncRNA ROR, a tumor oncogene associated with various human cancers, has been reported to be involved in regulating various cellular processes, such as proliferation, apoptosis and invasion through targeting multiple genes. However, the molecular biological function in bladder cancer has not been clearly elucidated. The aim of this study is to explore ROR expression levels and evaluated its function in bladder cancer. METHODS: LncRNA ROR expression levels in the 36 pairs of bladder cancer tissues (and corresponding non-tumor tissues) and bladder cancer cells were assessed by qRT-PCR. MTT assay, colony formation assay, flow cytometric analysis, wound healing assay, cell transwell assays, attachment/detachment and western blotting were performed to assess the effects of ROR on proliferation, apoptosis, migration/invasion and epithelial-to-mesenchymal (EMT) phenotypes in BC cells in vitro. ZEB1 is target of ROR. Rescue assays were performed to further confirm that ROR contributes to the progression of BC cells through targeting ZEB1. RESULTS: LncRNA ROR was up-regulated in bladder cancer tissues (compared to adjacent non-tumor tissues) and was almost overexpression in bladder cancer cells (compared with normal urothelial cell line SVHUC-1 cells). Increased lncRNA ROR expression significantly promoted tumor cells proliferation, inhibited cells apoptosis, facilitated cells metastasis and contributed to the formation of EMT phenotype. While down-regulated ROR could obviously inhibit cells proliferation, promote cells apoptosis, inhibit metastasis and reverse EMT to MET. ZEB1 was a target gene of ROR and was positive correlation with the level of ROR in cancer tissues. CONCLUSION: These results indicated that lncRNA ROR was associated with tumor progression in bladder cancer cells.CI - (c) 2017 The Author(s). Published by S. Karger AG, Basel.

BACKGROUND: Recent evidence has shown that long noncoding RNAs (lncRNAs) are involved in the process of epithelial-mesenchymal transition (EMT). However, little research has focused on the expression profile of lncRNAs during EMT in human lens epithelial cells (LECs) and their functions have not yet been described. METHODS: Dysregulated lncRNAs and mRNAs in normal human lens epithelial B-3(HLE B-3) cells and during transforming growth factor beta2(TGF-beta2)-induced EMT were analyzed via lncRNA microarray. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of differentially expressed mRNAs were performed to identify their functions and pathologic pathways. Six candidate lncRNAs were validated via quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR) to confirm the microarray data. RESULTS: A total of 775 lncRNAs (325 up-regulated and 450 down-regulated) and 935 mRNAs (329 up-regulated and 606 down-regulated) were differentially expressed in HLE B-3 cells during TGF-beta2-induced EMT compared to normal HLE B-3 cells. GO and KEGG pathway analyses indicated the functions of differentially expressed mRNAs in the TGF-beta2-induced EMT in HLE B-3 cells. qRT-PCR confirmed the trends indicated in microarray analysis for all 6 candidate lncRNAs. CONCLUSION: Our study lays the foundation for future research in lncRNAs related to EMT in HLE B-3 cells and could provide new avenues for the prevention and treatment of posterior capsule opacification (PCO).

Emerging evidence show that long noncoding RNAs (lncRNAs) play critical roles in tumor development. LincRNA-ROR (linc-ROR) is known to promote tumor progress in several human cancers, including hepatocellular carcinoma (HCC). Nevertheless, the roles of linc-ROR in HCC metastasis and its underlying mechanisms remain fully unclear. In the present study, we showed that linc-ROR was upregulated in HCC tissues and high linc-ROR expression level predicted poor prognosis. Functionally, linc-ROR significantly induced epithelial-mesenchymal transition (EMT), and increased in vitro invasion and in vivo metastasis of HCC cells. Mechanistically, linc-ROR acted as a sponge for miR-145 to de-repress the expression of target gene ZEB2, thereby inducing EMT and promoting HCC metastasis. Collectively, our research indicates the potential of linc-ROR as a vital therapeutic target for the treatment of aggressive and metastatic HCC.