Identification of a long non-coding RNA-associated RNP complex regulating metastasis at the translational step.
Long noncoding RNAs (lncRNAs) are a novel class of regulators that play crucial roles in development and disease. Here we highlight the findings by Huang and colleagues that a regulatory lncRNA (treRNA) acts as a scaffold for a new ribonucleic protein complex that inhibits translation of E-cadherin and promotes cell invasion. This work underscores the potential importance of lncRNAs in cancer metastasis. Genome-wide transcriptome sequencing efforts have led to the discovery of thousands of long noncoding RNAs (lncRNAs). LncRNAs are polyadenylated transcripts, typically more than 200 base pairs in length, that show polymerase II transcription initiation and elongation marks (Ulitsky and Bartel, 2013). Little is known about the biological roles of lncRNAs, but several potential mechanisms for the action of nuclear and cytoplasmic lncRNAs have been proposed. Nuclear lncRNAs mainly regulate the transcription of target genes by recruiting chromatinmodifying complexes to specific regions (Rinn and Chang, 2012), while cytoplasmic lncRNAs may interact with other RNAs, serve as molecular decoys for microRNAs and RNAbinding proteins, or function as cytoplasmic scaffolds of RNA–protein complexes. Interestingly, cytoplasmic lncRNAs may also interact with target mRNAs and protein complexes to regulate mRNA stability and translation (Carrieri et al, 2012; Yoon et al, 2012; Kretz et al, 2013). Recently, lncRNAs have been found to play important roles as drivers of tumour progression and as oncogenic suppressors in various cancer types. A report by Gumireddy et al (2013) in this issue now adds another lncRNA to this list by identifying a role for translational regulatory lncRNA (treRNA) in cellular invasion and metastasis. Gumireddy et al (2013) examined the expression of treRNA in matched primary and lymph node metastatic tumours and found higher treRNA levels in all metastatic tumours, suggesting that increased treRNA expression could be associated with metastasis. To investigate treRNA function, the authors ectopically expressed the lncRNA in the noninvasive breast cancer cell line MCF7 and observed increased cell migration and invasion capacity. Conversely, knockdown of treRNA in A549 cells (a metastatic cell line with high endogenous expression of treRNA) strongly suppressed cell migration and invasion. Using an in vivo bioluminescence system, the authors furthermore found that treRNAexpressing MCF7 cells promoted lung metastasis, while depletion of treRNA in A459 cells reduced the formation of lung tumours relative to controls, substantiating a potential role for treRNA in metastasis.