Taken together, our results suggest that PAB exerts anti-cancer activity in HCC cells through inhibition of STAT3, ERK1/2, Akt, and GSK-3β/β-catenin carcinogenic signaling pathways, and may be used as a phytomedicine in the treatment of HCC.
A sorafenib derivative and novel SHP-1 agonist, SC-59, acts synergistically with radiotherapy in hepatocellular carcinoma cells through inhibition of STAT3.
In conclusion, TUG1 interacting with miR-144 contributed to proliferation, migration and tumorigenesis through activation of the JAK2/STAT3 pathway in HCC.
IL-6 signaling was increased by Gab2 overexpression and impaired by Gab2 deletion <i>via</i> regulation of Jak2 and signal transducer and activator of transcription 3 phosphorylation and the expression of downstream genes, such as <i>Bcl-2</i> (B-cell lymphoma 2), <i>c-Myc</i>, <i>MMP7</i> (matrix metalloproteinase-7), and <i>cyclin D1</i><i>in vitro</i> and <i>in vivo</i> These data indicate that Gab2 mediates the pathologic progression of HCC by integrating multiple signaling pathways and suggest that Gab2 might be a powerful therapeutic target for HCC.-Cheng, J., Zhong, Y., Chen, S., Sun, Y., Huang, L., Kang, Y., Chen, B., Chen, G., Wang, F., Tian, Y., Liu, W., Feng, G.-S., Lu, Z. Gab2 mediates hepatocellular carcinogenesis by integrating multiple signaling pathways.
Human HCC cell lines HepG2 and Hep3B cells were transfected with pcDNA3.1(+)-EGFP-STAT3, STAT3 siRNA and HK2 siRNA, respectively, or treated with rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), and the effects on STAT3 and HK2 expression and cell glycolysis were determined.
Among these molecules, the protein levels of STAT3 were greatly enhanced in all hepatocyte nuclei and further elevated in the cytoplasm in HCC tissue samples at 18 months, and the levels of phosphorylated TP53 (p-p53-Ser 6 and -Ser 15) were increased in liver tissues.
Notably, expression levels of MAGEC2 and phosphorylated STAT3 are positively correlated and both are associated with incidence of metastasis in human hepatocellular carcinoma.
The inflammatory cytokines tumor necrosis factor-α and interleukin-6 and their downstream targets nuclear factor kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and signal transducer and activator of transcription 3 drive inflammation-associated HCC.
In conclusion, our findings have shown that the SNP rs111904020 (U/G) in STAT3 3'UTR acted as promotion factors in the HCC development through disrupting the regulatory role of miR-214 in STAT3 expression.
Dysregulation of Signal Transduction and Activator of Transcription-3 (STAT-3) was found along with related changes in STAT-3 targets which occurred in an etiology-dependent fashion in HCC-free cirrhosis.
Subsequently, Jak2 and Stat3 mRNA levels were detected by qPCR in hepatocarcinoma and paracancerous tissues, with their protein levels analyzed by Western blot after microRNA-409 was inhibited or up-regulated.