Fig. 1

The domain structure and signaling pathway of STAT3. a Schematic domain structure of STAT3. STAT3 is characterized by the presence of six different functional domains, including an amino-terminal domain (NTD) for cooperative binding of STAT proteins to multiple consensus DNA sites, a coiled-coil domain (CCD) for recruitment of STAT3 to the receptor as well as subsequent phosphorylation, dimerization and nuclear translocation, a DNA-binding domain (DBD) for recognizing and binding to a specific consensus DNA sequence, a linker domain for connecting the DBD with the SRC homology 2 (SH2) domain, a SH2 domain for recruitment and activation as well as dimerization of the STAT3 molecule by interacting with phosphorylated tyrosine residues in the opposing subunit, and a carboxyl-terminal transactivation domain (TAD). b STAT3 signaling pathway. STAT3 is activated by upstream growth factor kinases and cytokine receptors. Non-receptor tyrosine kinases such as SRC and ABL can also lead to constitutive activation of STAT3. Phosphorylated STAT3 dimerizes and translocates to nucleus, which causes the transcription of target genes including immunosuppression, angiogenesis, metastasis, proliferation and survival. The signaling pathway can be inhibited by SOCS proteins, PIAS proteins, and protein tyrosine phosphatases (PTPases), etc. c Interplay between noncoding RNAs and STAT3 signaling pathway. On the one hand, miRNAs and lncRNAs can regulate STAT3 activation through not only directly targeting STAT3, but also targeting the components of the STAT3 signaling pathway, such as IL-6, JAK2, SOCS1 and PIAS3; CircRNAs usually regulate STAT3 by acting as sponges for miRNAs. On the other hand, STAT3 is able to regulate miRNAs and lncRNAs expression in many ways.