We determined whether RPTS influences the interleukin-6 (IL-6)/Janus kinase (JAK)-signal transducer and activator of transcription-3 (STAT3) apoptosis molecular pathway and looked for colon cancer-related signal transduction pathways or targets inducing apoptosis.
Our data suggests that colon cancer cells are able to promote self-growth through the secretion of exosomes, especially under hypoxic conditions, which shortens mitosis duration and activates STAT3.
Growth hormone increased SHP-2/glycoprotein 130 binding and reduced interleukin 6-dependent STAT3 activation in the T84 human colon carcinoma and Jurkat human T-cell leukemia lines.
This therapeutic approach in colon cancer could mediate 5-FU chemoresistance via modulating therapeutic targets (ie, STAT3 and Nrf2 pathways) and decreased 5-FU-related adverse effects.
We found that rs744166 in STAT3 was associated with colon cancer risk in two studies; however, the direction of the observation was reversed in TP53 mutant tumors possibly due to a nullification of the effect by mutant p53.
Taken together, our results suggest that the BMP-2 induced STAT3-mediated induction of colon cancer cell metastasis requires an EMT and/or changes in CSC markers.
Furthermore, high mRNA expression levels of Stat3 or Jab1 in colon cancer, breast cancer and glioblastoma are associated with significantly shorter survival times from the R2 online database.
This suggests that STAT3 pathways might constitute attractive pharmaceutical targets in colon cancer patients where anti-EGF receptor drugs are ineffective.
Functional studies showed that increasing miR-27a inhibited colon cancer cell proliferation, promoted apoptosis and attenuated cell migration, which were also linked to downregulation of p-STAT3 and upregulation of cleaved caspase 3.
Using STAT3-null human colon carcinoma cell line A4 cells, we generated seven mutants of STAT3 bearing single mutations clinically identified in AD-HIES patients' cells and studied the functional loss of these mutants in IL- 6-Jak/STAT3 signalling pathway.
In conclusion, p-STAT3 may participate in the progression of the early stage of colon cancer through the up-regulation of CD133, which in turn induces survivin expression.
In our study, we showed that microRNA-1299 (miR-1299) was closely related to the TNM stage of colon cancer, and that the expression of miR-1299 was negatively correlated with the expression of STAT3 in colon cancer which means that miR-1299 can be a negative regulator of STAT3 in colon cancer.
In conclusion, our study suggested that MC-LR promoted the progression of colon carcinoma, at least in part, by regulating the expression miR-221, PTEN and STAT3 phosphorylation, which offers a novel perspective to understand the connection between MC-LR and colon cancer.