Quaking 5 suppresses TGF-?-induced EMT and cell invasion in lung adenocarcinoma

ABSTRACT: Quaking (QKI) proteins belong to the signal transduction and activation of RNA (STAR) family of RNA-binding proteins that have multiple functions in RNA biology. Here, we show that QKI-5 is dramatically decreased in metastatic lung adenocarcinoma (LUAD). QKI-5 overexpression inhibits TGF-?-induced epithelial-mesenchymal transition (EMT) and invasion, whereas QKI-5 knockdown has the opposite effect. QKI-5 overexpression and silencing suppresses and promotes TGF-?-stimulated metastasis in vivo, respectively. QKI-5 inhibits TGF-?-induced EMT and invasion in a TGF?R1-dependent manner. KLF6 knockdown increases TGF?R1 expression and promotes TGF-?-induced EMT, which is partly abrogated by QKI-5 overexpression. Mechanistically, QKI-5 directly interacts with the TGF?R1 3' UTR and causes post-transcriptional degradation of TGF?R1 mRNA, thereby inhibiting TGF-?-induced SMAD3 phosphorylation and TGF-?/SMAD signaling. QKI-5 is positively regulated by KLF6 at the transcriptional level. In LUAD tissues, KLF6 is lowly expressed and positively correlated with QKI-5 expression, while TGF?R1 expression is upregulated and inversely correlated with QKI-5 expression. We reveal a novel mechanism by which KLF6 transcriptionally regulates QKI-5 and suggest that targeting the KLF6/QKI-5/TGF?R1 axis is a promising targeting strategy for metastatic LUAD.

SUBMITTER: Prof. Hong-Tao Zhang 

PROVIDER: S-SCDT-EMBOR-2020-52079V1 | biostudies-other |

REPOSITORIES: biostudies-other