ABSTRACT
Alu sequences are the most abundant short interspersed repeated elements in the human genome. Here we show that in a cell culture model of colorectal cancer (CRC) progression, we observe accumulation of Alu RNA that is associated with reduced DICER1 levels. Alu RNA induces epithelial-to-mesenchymal transition (EMT) by acting as a molecular sponge of miR-566. Moreover, Alu RNA accumulates as consequence of DICER1 deficit in colorectal, ovarian, renal and breast cancer cell lines. Interestingly, Alu RNA knockdown prevents DICER1 depletion-induced EMT despite global microRNA (miRNA) downregulation. Alu RNA expression is also induced by transforming growth factor-ß1, a major driver of EMT. Corroborating this data, we found that non-coding Alu RNA significantly correlates with tumor progression in human CRC patients. Together, these findings reveal an unexpected DICER1-dependent, miRNA-independent role of Alu RNA in cancer progression that could bring mobile element transcripts in the fields of cancer therapeutic and prognosis.
Subject(s)
Alu Elements/genetics , Colorectal Neoplasms/genetics , DEAD-box RNA Helicases/metabolism , Epithelial-Mesenchymal Transition/genetics , MicroRNAs/genetics , Ribonuclease III/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Colon/pathology , Colorectal Neoplasms/pathology , DEAD-box RNA Helicases/genetics , Disease Progression , Down-Regulation , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Liver/pathology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/secondary , MicroRNAs/metabolism , RNA/metabolism , Ribonuclease III/genetics , Transforming Growth Factor beta1/metabolismABSTRACT
The authors present a case of sigma infarction. They examine the etiopathogenesis, underline the clinical and instrumental signs and discurs the vascular anatomy and diagnostic difficulties. Operation is considered to be necessary to reduce the severe of prognosis.
