Introduction: The functions of large non-coding RNAs (ncRNA) have remained elusive in many cases. MALAT-1 (Metastasis-Associated-in-Lung-Adenocarcinoma-Transcript-1) is a ncRNA, that is highly expressed in several tumor types. Methods: Overexpression and RNA interference (RNAi) approaches were used for the analysis of the biological functions of MALAT-1 RNA. Tumor growth was studied in nude mice. For prognostic analysis MALAT-1 RNA was detected on paraffin embedded lung cancer tissue probes (n=352) using in-situ hybridization. Results: MALAT-1 was highly expressed in several human non-small cell lung cancer cell lines. MALAT-1 expression was regulated by an endogenous negative feedback loop. In A549 NSCLC cells, RNAi mediated suppression of MALAT-1 RNA suppressed migration and clonogenic growth. Forced expression of MALAT-1 in NIH 3T3 cells significantly increased migration. Upon injection into nude mice, NSCLC xenografts with decreased MALAT-1 expression were impaired in tumor formation and growth. In-situ hybridization on paraffin embedded lung cancer tissue probes revealed that high MALAT-1 RNA expression in squamous cell carcinoma of the lung was associated with a poor prognosis. Conclusions: These data indicate that MALAT-1 expression levels are associated with patient survival and identify tumor promoting functions of MALAT-1.
Schmidt et al. (Thu,) studied this question.