MiR-577 Regulates TGF-? Induced Cancer Progression through a SDPR-Modulated Positive-Feedback Loop with ERK-NF-?B in Gastric Cancer.

ABSTRACT: Transforming growth factor ? (TGF-?) drives epithelial-mesenchymal transition (EMT), playing vital roles in cancer metastasis. The crosstalk between microRNAs (miRNAs) and TGF-? are frequently observed and involved in TGF-?-induced EMT. Here, we determine that miR-577 is significantly upregulated in gastric cancer (GC). miR-577 expression is positively correlated with GC metastasis status and poor patient prognosis. Functional assays demonstrate that miR-577 promotes metastasis and chemoresistance by inducing EMT and stemness-like properties. Moreover, TGF-? promotes the expression of miR-577, and miR-577 participates TGF-?-mediated cancer metastasis. Mechanistically, TGF-? activates miR-577 via NF-?B-mediated transcription, and miR-577 enhances TGF-? signaling by targeting the serum deprivation protein response (SDPR), which directly interacts with ERK to inactivate the ERK-NF-?B pathway, hence forming a feedback loop to drive tumor metastasis. A plausible mechanism of EMT induction by the TGF-? network is elucidated. Our findings suggest that the TGF-?-miR-577-SDPR axis may be a potential prognostic marker and therapeutic target against cancer metastasis in GC.

SUBMITTER: Luo Y 

PROVIDER: S-EPMC6554531 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature