The Importance of Tumor Necrosis Factor-<i>α</i>-Induced Protein-8 Like-2 in the Pathogenesis of Cervical Cancer and Preeclampsia via Regulation of Cell Invasion

The Importance of Tumor Necrosis Factor-α-Induced Protein-8 Like-2 in the Pathogenesis of Cervical Cancer and Preeclampsia via Regulation of Cell Invasion

Hong Zhang,¹ Wen-Jun Han² and Zhi-Lei Zhang²

¹Department of Obstetrics, Yantaishan Hospital, Yantai, Shandong, China
²Department of Gynecology, Qingdao Women and Children’s Hospital, Qingdao, Shandong, China

Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) as a novel negative immune regulator plays an important role in several human diseases. However, its influences in cervical cancer and preeclampsia (PE) remain unclear. This study aims to explore the important role of TIPE2 in cervical cancer and PE via regulating cell invasion. TIPE2 expression in the cervical cancer tissues or the placenta of PE patients was detected. Human cervical cancer cell lines and trophoblasts were transfected with adenovirus expressing human TIPE2 and green fluorescent protein (GFP) (Ad-TIPE2), or the control adenovirus expressing GFP (Ad-GFP). Xenograft models were also constructed on nude mice, aiming to clarify how TIPE2 affects in vivo growth of cervical cancer cells. TIPE2 was down-regulated in the tumor tissues or placenta of patients with cervical cancer or PE. As a result, CaSKi and Hela cells in the Ad-TIPE2 group had decreased migration and invasion, with significant up-regulations of TIPE2 and E-cadherin, but down-regulations of β-catenin and N-cadherin. Ad-TIPE2 decreased the volume and weight of xenograft tumors in the nude mice, with the down-regulation of Ki67. The quantity of cells (HTR8/SVneo and JEG3 cells) transfected with Ad-TIPE2 had increased, with up-regulations of TIPE2, matrix metalloproteinase (MMP)-2 and MMP-9. TIPE2 overexpression could reduce the invasion and migration of cervical cancer cells via inhibiting the epithelial-mesenchymal transition (EMT) process, and promote trophocyte invasion via upregulating the expression of MMPs, and it may be used as a potential therapeutic target for cervical cancer and PE.

Keywords —— β-catenin; cervical cancer; epithelial-mesenchymal transition; preeclampsia; TIPE2

===============================

Tohoku J. Exp. Med 2022, 257, 181-191.

Correspondence: Zhi-Lei Zhang, Department of Gynecology, Qingdao Women and Children’s Hospital, No. 217, Liaoyang West Road, Shibei District, Qingdao, Shandong 266011, China.

e-mail: zzzhang_1216@126.com