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

Lv,Qiongying; Wu,Kejia; Liu,Fulin; Wu,Wanrong; Chen,Yurou; Zhang,Wei

doi:10.3892/ijo.2018.4503

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

Authors:
- Qiongying Lv
- Kejia Wu
- Fulin Liu
- Wanrong Wu
- Yurou Chen
- Wei Zhang
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Affiliations: Department of Gynaecology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China, The First Department of Gynaecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: July 26, 2018 https://doi.org/10.3892/ijo.2018.4503
Pages: 1809-1817

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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.

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