MUC1-C Induces the LIN28B→LET-7→HMGA2 Axis to Regulate Self-Renewal in NSCLC.

ABSTRACT:

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The LIN28B→let-7 pathway contributes to regulation of the epithelial-mesenchymal transition (EMT) and stem cell self-renewal. The oncogenic MUC1-C transmembrane protein is aberrantly overexpressed in lung and other carcinomas; however, there is no known association between MUC1-C and the LIN28B→let-7 pathway. Here in non-small cell lung cancer (NSCLC), silencing MUC1-C downregulates the RNA-binding protein LIN28B and coordinately increases the miRNA let-7. Targeting MUC1-C function with a dominant-negative mutant or a peptide inhibitor provided confirming evidence that MUC1-C induces LIN28B→let-7 signaling. Mechanistically, MUC1-C promotes NF-κB p65 chromatin occupancy of the LIN28B first intron and activates LIN28B transcription, which is associated with suppression of

SUBMITTER: Alam M 

PROVIDER: S-EPMC4369171 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature