Aberrant shuttling of long noncoding RNAs during the mitochondria-nuclear crosstalk in hepatocellular carcinoma cells.

There is intense crosstalk between mitochondria and the nucleus that is mediated by proteins and long noncoding RNAs (lncRNAs). Using a modified RNA fluorescent in situ hybridization (RNA-FISH) assay coupled with MitoTracker staining, we tracked the mitochondrial localization of lncRNAs, including lncND6 and lncCytB. The nuclear genome-transcribed lncRNA MALAT1 was enriched in the mitochondria of hepatocellular carcinoma cells. Knockdown of MALAT1 significantly impaired mitochondrial function and alter tumor phenotype in HepG2 cells. The localization of the mitochondria-encoded lncRNA lncCytB was also abnormal in HepG2 cells. In normal hepatic HL7702 cells, lncCytB was located in mitochondria, but in HepG2 cells, it was enriched considerably in the nucleus. These data suggest that aberrant shuttling of lncRNAs, whether nuclear genome-encoded or mitochondrial genome-transcribed, may play a critical role in abnormal mitochondrial metabolism in cancer cells. This data lays the foundation for further clarifying the roles of mitochondria-associated lncRNAs in cancers.