Department of Pathology, Eastern Hospital, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu, 610101, China.
Department of Thoracic Surgery, Eastern Hospital, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu, 610101, China.
BMC Cancer. 2023 Nov 20;23(1):1128. doi: 10.1186/s12885-023-11639-y.
The roles of low molecular mass polypeptide 2 (LMP2) and transporter-associated with antigen processing (TAP2) in tumorigenesis are controversial. Here we aimed to explore the effect of LMP2 and TAP2 on the oncogenesis and metastasis of cervical cancer cells.
The expressions of LMP2 and TAP2 in cervical cancer and normal tissues were determined by qPCR. Plate colony formation, cell counting kit-8 analysis and in vivo tumor xenograft assays were used to detect the tumor growth. Wound healing and transwell assays were used to detect the metastasis of cervical cancer. Gelatin zymography and western blotting assays were used to detect the effect of LMP2 and TAP2 on the EMT and Wnt/β-catenin pathway in cervical cancer cells.
In the present study, we reported that LMP2 and TAP2 levels were overexpressed in cervical cancer. Overexpression of LMP2 and TAP2 impaired the proliferation of Hela cells. In vivo studies substantiated that LMP2 and TAP2 antagonized tumor growth. Likewise, LMP2 and TAP2 overexpression decreased the migration and invasion ability of Hela cells by regulating the process of epithelial-mesenchymal transition (EMT). Mechanically, LMP2 and TAP2 subverted the protein abundance of Wnt1 and β-catenin, thereby downregulating their downstream targets Cyclin D1 and c-Myc. In addition, Wnt1 overexpression partially rescued the observed consequences of ectopic expression of LMP2 and TAP2 in cervical cancer cells. Taken together, our study revealed that LMP2 and TAP2 suppress the oncogenesis and metastasis of cervical cancer cells by Wnt/β-catenin pathway and altering EMT.
LMP2 and TAP2 may inhibit the oncogenesis and metastasis of cervical cancer cells by inhibiting the process of EMT and the Wnt/β-catenin signaling pathway, which may provide important insight into prospective targets for the treatment of cervical cancer.
低分子量多肽 2（LMP2）和抗原加工相关转运体（TAP2）在肿瘤发生中的作用存在争议。在这里，我们旨在探讨 LMP2 和 TAP2 对宫颈癌发生和转移的影响。
通过 qPCR 检测宫颈癌和正常组织中 LMP2 和 TAP2 的表达。平板集落形成、细胞计数试剂盒-8 分析和体内肿瘤异种移植实验用于检测肿瘤生长。划痕愈合和 Transwell 实验用于检测宫颈癌的转移。明胶酶谱和 Western blot 实验用于检测 LMP2 和 TAP2 对宫颈癌细胞 EMT 和 Wnt/β-catenin 通路的影响。
在本研究中，我们报道 LMP2 和 TAP2 水平在宫颈癌中过表达。LMP2 和 TAP2 的过表达抑制了 Hela 细胞的增殖。体内研究证实 LMP2 和 TAP2 拮抗肿瘤生长。同样，LMP2 和 TAP2 的过表达通过调节上皮-间充质转化（EMT）过程降低了 Hela 细胞的迁移和侵袭能力。机制上，LMP2 和 TAP2 使 Wnt1 和 β-catenin 的蛋白丰度发生逆转，从而下调其下游靶标 Cyclin D1 和 c-Myc。此外，Wnt1 的过表达部分挽救了 LMP2 和 TAP2 在宫颈癌细胞中过表达所观察到的后果。综上所述，我们的研究表明，LMP2 和 TAP2 通过 Wnt/β-catenin 通路和改变 EMT 抑制宫颈癌的发生和转移。
LMP2 和 TAP2 通过抑制 EMT 过程和 Wnt/β-catenin 信号通路抑制宫颈癌的发生和转移，这可能为宫颈癌的治疗提供重要的潜在靶点。
