| Breast cancer is one of the most common cancers worldwide in women. In China, theincidence of breast cancer has soared rapidly in recent years. Not carcinoma in situ but distantmetastasis is a major cause of poor survival and death. Recent years,the rates of metastasisand mortality in breast cancer patients have decreased as a result of early diagnosis bymammographic screening and the implementation of systemic adjuvant therapy. Research onbreast cancer metastasis mechanism contributes to early molecular diagnosis, and provides uswith the scientific theoretical basis the implementation of systemic adjuvant therapy.Epithelial–mesenchymal transition (EMT) is a key step during embryogenesis. Cellcharacteristics are highly affected during EMT, resulting in altered cell-cell and cell-matrixinteractions, cell motility and invasiveness. Accumulating evidence suggests a critical role incancer progression. EMT has been considered to be a mainly course of cancer metastasismechanism. Multiple transcription factors have been found disregulated expressed in cancers,such as Snail, Slug, Twist, ZEB1and ZEB2. ect. Which can induce EMT and contribute tocancer metastasis and invasion. Signal transduction pathways such as tumormicroenvironment, TGF-β,Wnt, Notch and Hedgehog can also coordinate EMT programs.Emerging data suggest extensive crosstalks among different regulation factors, allowing themto form an intricate network that is responsible for regulating cancer progression. The cancerstem cells hypothesis (CSCs) believes that CSCs are essential for cancer metastasis.Considered EMT process can generate CSC-like cells, EMT has been to be considered to be anecessary key step of cancer metastasis.Non-coding RNA (ncRNA) is a kind of genome transcript with little protein-codingpotential. Accroding to the lengthof ncRNA, it can be mainly classified as small ncRNA andlncRNA. The role of miRNAs, a kind of small ncRNA have been drawing more attentionsincancer progress. Multiple miRNAs have been found playing a role in regulating EMT andcancer metastasis, such as miR-200family, let-7, miR-34, miR-205.ect. The longnon-coding RNAs (lncRNAs) are RNA molecules over200nt in length with littleprotein-coding potential. Recently, ten thousands of lncRNAs have been discovered with thedevelopment of high-throughput sequencing.Recent studies have revealed that lncRNAs areinvolved in regulation of multiple biological processes, including development,differentiation and carcinogenesis. With the research on the functions and mechanisms oflncRNAs, more and more attention have been payed to the role of lncRNAs in cancer process.While the specific species of lncRNAs that participate in cancer progression remain unknown.In this article, we showed linc-ROR was significantly upregulated in breast cancer cells,as well as in the clinical breast cancer tissue samples compared to the normal tissues or normalcells. ectopic overexpression of linc-ROR in immortalized human mammary epithelial cellsinduced an EMT program.Moreover, we showed that linc-ROR enhanced breast cancer cellmigration 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 andfunctioned as a competing endogenous RNA to miR-205. Specifically, linc-ROR preventedthe degradation of miR-205target genes, including the EMT inducer ZEB2.Our results indicate that linc-ROR functions as a new regulator of EMT and can promotebreast cancer progression and metastasis through regulation of miR-205. Potentially, thefindings of this study implicate the relevance of linc-ROR as a possible therapeutic target foraggressive and metastatic breast cancers. |
PDF Full Text Request