Interleukin‑17A and heparanase promote angiogenesis and cell proliferation and invasion in cervical cancer

Abstract

Interleukin‑17A (IL‑17A) is a CD4 T-cell-derived pro-inflammatory cytokine that is involved in human cervical tumorigenesis. Heparanase (HPSE) is an endo-glycosidase expressed in mammals, which has been confirmed to be associated with cervical cancer invasion. In the present study, it was hypothesized that IL‑17A and HPSE are key proteins promoting tumor angiogenesis and cell proliferation and invasion in cervical cancer. The expression of IL‑17A and HPSE in cervical cancer tissues was detected by immunohistochemical staining. In addition, the expression of IL‑17A and HPSE was down- and upregulated via RNAi and human recombinant proteins, and MTT and Transwell assays were performed to examine cervical cancer cell proliferation and invasion, respectively. Flow cytometry analysis was also performed to detect cell cycle distribution, and the levels of target mRNA and protein were evaluated by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. IL‑17A and HPSE were highly expressed in cervical cancer tissues, and microvessel density was notably higher in the IL‑17A-positive group. IL‑17A and/or HPSE recombinant protein promoted the proliferation and invasion of cervical cancer cells, increased the proportion of cells in the G2/M phase, and enhanced the mRNA and protein expression of human papillomavirus E6, P53, vascular endothelial growth factor and CD31, whereas downregulation of IL‑17A and/or HPSE exerted the opposite effects. Furthermore, downregulation of IL‑17A and/or HPSE was found to inhibit the expression of nuclear factor (NF)-κB P65. In summary, IL‑17A and HPSE may promote tumor angiogenesis and cell proliferation and invasion in cervical cancer, possibly via the NF-κB signaling pathway. These findings may lead to the identification of new diagnostic markers and therapeutic targets.

Impact of sustained TGFβ receptor inhibition on chromatin accessibility and gene expression in cultured human endometrial MSC

“…In keeping with previous observations, 43 genes involved in angiogenesis (e.g. SLIT2, HPSE and SFRP1), [51][52][53] cell survival (e.g. ENPP2, FAIM2), 54,55 and immunomodulation (e.g.…”

IL‐25 promotes cisplatin resistance of lung cancer cells by activating NF‐κB signaling pathway to increase of major vault protein

“…IL‐25 is an NF‐κB signaling pathway activator participating in multiple physiological processes of tumor cell, such as proliferation, apoptosis, and metastasis . Therefore, we supposed that IL‐25 mediates MVP expression by activating NF‐κB signaling pathway.…”

“…IL-25 is an NF-κB signaling pathway activator participating in multiple physiological processes of tumor cell, such as proliferation, apoptosis, and metastasis. 32,33 Therefore, we supposed that IL-25 mediates MVP expression by activating NF-κB signaling pathway. To confirm our hypothesis, we detected the expression of NF-κB signaling pathway-associated proteins by western blot in IL-25 overexpressed and silenced cells.…”

The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment

“…These factors play an essential role in the occurrence and development of tumors and promote the growth and metastasis of tumors. Inflammation leads to cell transformation, and the tumor cells and their surrounding interstitium secrete cytokines and chemical activators, forming a positive cycle between cancer and inflammation, which is conducive to the communication 2 BioMed Research International between tumors and the host stroma, thus accelerating the progression of tumors [49,50]. TNF-α is a special and multifunctional cytokine that plays a key role in immune regulation, the inflammatory response, and defense [51].…”