Related Experiment Video
Updated: May 12, 2026

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
Metastasis suppressor Nm23-H1 inhibits STAT3 signaling via a negative feedback mechanism
Lei Gong1, Zhihao Wu, Lili Guo
1Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Anshan Road No 154, Heping District, Tianjin 300052, China.
Abstract:
Persistent STAT3 activation is a critical event in tumorigenesis and metastatic progression. Recent studies have found higher levels of STAT3 in metastatic tissues than in primary tumor tissues. We speculated that such increased STAT3 activity might be attributed to a loss of function or reduction in expression of metastasis inhibitory protein during cancer progression, and we therefore examined the role of tumor metastasis-suppressor nm23-H1 in the activation of STAT3 in the A549 lung cancer cell line. We found that IL-6-dependent induction of tyrosine phosphorylation and activation of STAT3 were influenced by nm23-H1 inhibition. IL-6-induced STAT3(Tyr705) phosphorylation was significantly enhanced in A549 cells transfected with siRNA specific for nm23-H1, and the effect of nm23-H1 depletion on IL-6-induced STAT3(Tyr705) phosphorylation was reversed by ectopic expression of shRNA-resistant nm23-H1 protein. Moreover, STAT3 directly bound to the STAT3 binding site on the nm23-H1 promoter and activated its expression. Thus, we have identified a new feedback mechanism that might provide insight into an in-built metastasis-suppression function in tumor cells and which could be a logical new target for treatment of early metastatic disease.
More Related Videos
Related Concept Videos
Abnormal Proliferation
The JAK-STAT Signaling Pathway
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
MicroRNAs
MicroRNAs

