ausblenden:
Schlagwörter:
Animals
Female
*Gene Expression Regulation, Neoplastic
HEK293 Cells
Humans
Mice
Mice, Inbred NOD
Mice, SCID
Multiprotein Complexes/metabolism/physiology
Neoplasm Metastasis/*genetics
Protein Binding
Protein Biosynthesis/*genetics
RNA, Long Noncoding/*metabolism/physiology
Ribonucleoproteins/genetics/isolation & purification/metabolism/*physiology
Tumor Cells, Cultured
Zusammenfassung:
Long non-coding RNAs (lncRNAs) are a novel class of regulatory genes that play critical roles in various processes ranging from normal development to human diseases such as cancer progression. Recent studies have shown that lncRNAs regulate the gene expression by chromatin remodelling, transcription, splicing and RNA decay control, enhancer function, and epigenetic regulation. However, little is known about translation regulation by lncRNAs. We identified a translational regulatory lncRNA (treRNA) through genome-wide computational analysis. We found that treRNA is upregulated in paired clinical breast cancer primary and lymph-node metastasis samples, and that its expression stimulates tumour invasion in vitro and metastasis in vivo. Interestingly, we found that treRNA downregulates the expression of the epithelial marker E-cadherin by suppressing the translation of its mRNA. We identified a novel ribonucleoprotein (RNP) complex, consisting of RNA-binding proteins (hnRNP K, FXR1, and FXR2), PUF60 and SF3B3, that is required for this treRNA functions. Translational suppression by treRNA is dependent on the 3'UTR of the E-cadherin mRNA. Taken together, our study indicates a novel mechanism of gene regulation by lncRNAs in cancer progression.
