Interleukin-6 Promotes Cervical Cancer Development Through Janus Kinase 2/Signal Transducer and Activator of Transcription 6 Signaling Pathway

Abstract

Interleukin (IL)-6 regulates several cellular processes such as proliferation, differentiation and immune regulation. The pathogenesis of cervical cancer is closely related to abnormal secretion and regulation of cytokines. IL-6 in the pathogenesis of cervical cancer was investigated in the present study. In our work, we collected cervical cancer tissues and adjacent normal tissues first and then established mouse model of cervical cancer for following assays. Immunohistochemistry and Western blot analysis were performed to detect IL-6, JAK3 and STAT6 and qRT-PCR determined VEGF, MMP-2, MMP-9 and others in adjacent tissues and cancer tissues. MTT was used to detect the capability of proliferation, invasion and migration. Chromatin immunoprecipitation was employed to verify the binding of STAT6 to IL-6. The effect of STAT6 inhibitors, AS1517499 on JAK3/STAT6 axis was also detected through in vivo experiments. Except IL-6, the related proteins were upregulated in cervical cancer tissues. IL-6 (25–100 ng/mL) accelerated the growth of Hela cells. IL-6 improved cell migratory and invasive ability when recombinant IL-6 promoted phosphory-lation and JAK3/STAT6. The activity of IL-6 in Hela was mediated by JAK3/STAT6 signaling pathway as AS1517499 inhibited IL-6-induced JAK3/STAT6 phosphorylation and STAT6 bound to the IL-6 promoter. STAT6 inhibitors significantly suppressed tumor growth and reduced p-STAT3 level. IL-6 contributes to cervical cancer through JAK3/STAT6 signaling which could be a cornerstone of subsequent anti-cervical cancer treatment.

Comparative transcriptome analysis of endothelial progenitor cells of HbSS patients with and without proliferative retinopathy

“…43 Furthermore, IL-6 has been shown to contribute to the development of cervical cancer through JAK-3/STAT6 signaling (Janus Kinase-3/signal transducer and activator of the STAT6 signaling pathway). 33 Interestingly, RAB3C , IL-6 , and STAT6 are up-regulated in RNA-Seq analysis when the groups with and without PSCR are compared. These data may indicate that signaling pathways including such genes may be associated with important pathways that participate in the development of PSCR, such as proliferation, migration, and angiogenesis.…”

“…These pathways play a key role in supporting the transmission of signals from receptor tyrosine kinases (RTKs) to the nucleus. [32][33][34] MAP kinases are enzymes present in MAPK cascades. In most cells, MAPKs are part of a group of cytoplasmic enzymes that transmit mitogenic and cell differentiation signals.…”

“…These pathways play a key role in supporting the transmission of signals from receptor tyrosine kinases (RTKs) to the nucleus. 32–34…”

Qingfei Tongluo Mixture Attenuates Bleomycin-Induced Pulmonary Inflammation and Fibrosis through mTOR-Dependent Autophagy in Rats

“…Autophagy is involved in the activation of lung fibroblasts and interstitial transformation of human pulmonary bronchial epithelial cells, regulating the secretion of various cytokines, and promoting and inhibiting the development of fibrosis by regulating oxidative stress in the process of pulmonary fibrosis [8]. Published research has found that traditional Chinese medicine, such as Ligustrazin [62], Fu-Zheng-Tong-Luo formula [63], Number 2 Feibi recipe [64], can reduce oxidative stress in lung tissue, promote autophagy, and therefore slow or inhibit the degree of pulmonary fibrosis. As mentioned above, compared to the model group, rats in the QFTL-L group showed a significant decrease in HYP levels (Figure 3(e)) and α-SMA protein expression (Figures 4(b), 4(d), and 4(e)), but the addition of CQ blocked the trend of improvement.…”