Angiotensin II (Ang II) has been shown to function as a key role in neovascularization of hepatocellular carcinoma (HCC), but little is known its underlying mechanisms. The aim of this study was to explore the role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in Ang II-induced HCC angiogenic factors production. Herein, we found that Ang II upregulated angiogenic factors production such as vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and Tie-2 in MHCC97H cells in a time- and concentration-dependent manner. And VEGF and Ang-2 caused a significant increase in angiogenic tube formation. Especially, Ang II-induced angiogenic tube formation was blunted by VEGF small interfering RNA (siRNA) and Ang-2 siRNA, respectively. The JAK2 inhibitor AG490 partly attenuated the effects of Ang II. Moreover, Ang II- induced JAK2 and STAT3 phosphorylation was significantly suppressed by losartan but not PD123319. Meanwhile, STAT3 phosphorylation and suppressor of cytokine signaling 3 (SOCS3) expression induced by Ang II were evidently impaired by AG490. More importantly, SOCS3 siRNA remarkably reinforced Ang II-induced VEGF, Ang-2 and Tie-2 generation in MHCC97H cells. Taken together, the present study demonstrates that Ang II induces angiogenic factors production partly via AT1/ JAK2/STAT3/SOCS3 signaling pathway in MHCC97H cells. These findings may provide important insights into the potential mechanism with respect to the AT1/ JAK2/ STAT3/SOCS3 signaling pathway associated with Ang II-induced angiogenesis in the pathogenesis of HCC.
Gastric cancer (GC) is one of the most prevalent malignant types worldwide, especially in East Asia. Due to its frequently advanced stage at diagnosis, the mortality from GC is high and the prognosis is still unsatisfactory. Thus, early detection using effective screening approaches is vital to decrease the morbidity and mortality of GC. Interestingly, biomarkers can be used for diagnosis, prediction of sensitivity to treatment, and prognosis in GC. The potential biomarkers detectable in liquid biopsies such as circulating tumor cells (CTCs), long non-coding RNAs (lncRNAs), cell-free DNA (cfDNA), microRNAs, and exosomes reveal numerous information regarding the early prediction and the outcomes for GC patients. Additionally, using the novel serum biomarkers has opened up new opportunities for diagnosing and monitoring patients with GC. This review mainly summarizes the novel progress and approaches in GC biomarkers, which could be potentially used for early diagnosis and therapy monitoring. Meanwhile, we also discussed the advantages, disadvantages, and future perspectives of GC biomarkers.
14 October 2021 in World Journal of Gastroenterology