Abstract

Transmembrane proteins (TMEMs), spanning the entire width of lipid bilayers and anchored to them permanently, exist in diverse cell types to implement a series of essential physiological functions. Recently, TMEM48, a member of the TMEM family, has been demonstrated to be closely associated with tumorigenesis. However, little is known about the specific role of TMEM48 in cervical cancer (CC). This study aimed to investigate the biological functions of TMEM48 in CC. The CCK-8 assay was performed to detect CC cell proliferation. The wound healing and transwell assays were conducted to measure cell migration and invasion, respectively. The levels of TMEM48, β-catenin, T cell factor 1(TCF1) and axis formation inhibitor 2 (AXIN2) were examined by the western blot analysis. Xenograft models were established for the tumorigenesis assay in vivo. The results showed that TMEM48 was overexpressed in CC tissues and cell lines. Knockdown of TMEM48 significantly inhibited CC cell proliferation, migration and invasion in vitro and suppressed CC cell growth in vivo. In addition, the investigation on the molecular mechanisms indicated that TMEM48 down-regulation remarkably decreased the protein levels of β-catenin, TCF1 and AXIN2 in CC cells and TMEM48 exerted its promoting effect on CC progression via activation of the Wnt/β-catenin pathway. Taken together, our study suggested TMEM48 as a promising therapeutic target for CC treatment.

摘要

跨膜蛋白 (TMEMs) 跨越脂双层的整个宽度并永久锚定在它们上，存在于不同的细胞类型中，以实现一系列基本的生理功能。最近，TMEM 家族的成员 TMEM48 已被证明与肿瘤发生密切相关。然而，关于 TMEM48 在宫颈癌 (CC) 中的具体作用知之甚少。本研究旨在研究 TMEM48 在 CC 中的生物学功能。进行CCK-8测定以检测CC细胞增殖。进行伤口愈合和 transwell 试验以分别测量细胞迁移和侵袭。通过蛋白质印迹分析检查 TMEM48、β-连环蛋白、T 细胞因子 1（TCF1）和轴形成抑制剂 2（AXIN2）的水平。为肿瘤发生测定建立异种移植模型体内。结果显示TMEM48在CC组织和细胞系中过表达。敲除 TMEM48 可显着抑制体外CC 细胞增殖、迁移和侵袭，并抑制体内CC 细胞生长。此外，分子机制研究表明，TMEM48下调显着降低CC细胞中β-catenin、TCF1和AXIN2的蛋白水平，TMEM48通过激活Wnt/β-catenin通路对CC进展发挥促进作用。. 总之，我们的研究表明 TMEM48 作为 CC 治疗的有希望的治疗靶点。