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PRAME通过Wnt/β-连环蛋白信号通路调控促进宫颈癌的增殖和迁移。

PRAME Promotes Cervical Cancer Proliferation and Migration via Wnt/β-Catenin Pathway Regulation.

作者信息

Chen Xin, Jiang Mengying, Zhou Shengjie, Chen Hong, Song Gendi, Wu Yichen, Zhu Xueqiong

机构信息

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China.

Department of Obstetrics and Gynecology, Taizhou Women and Children's Hospital of Wenzhou Medical University, Taizhou 318000, China.

出版信息

Cancers (Basel). 2023 Mar 16;15(6):1801. doi: 10.3390/cancers15061801.

Abstract

A significant burden is placed on the lives of females due to cervical cancer, which is currently the leading cause of cancer death among women. Preferentially expressed antigen in melanoma (PRAME) belongs to the CTA gene family and was found to be abnormally expressed among different types of cancers. Our previous research also indicated that PRAME was highly expressed in cervical cancer compared with normal tissues. However, the roles and detailed mechanisms of PRAME have not been explored in cervical cancer. In the present study, the expression of PRAME in cervical tissues and cells was detected by immunohistochemistry (IHC), qRT-PCR, and Western blotting. Additionally, CCK-8, BrdU, scratch, transwell, and flow cytometry assays were conducted to explore the function of PRAME in regulating the malignant biological behaviors of cervical cancer cells. Nude mice were used to confirm the role of PRAME in tumor growth in vivo. Furthermore, the Wnt inhibitor MSAB was used to verify the role of PRAME in regulating the Wnt/β-catenin pathway both in vitro and in vivo. The results of IHC, qRT-PCR, and Western blotting showed that PRAME was highly expressed in cervical cancer tissues and cells. PRAME knockdown attenuated cell growth, migration, and invasion; induced G0/G1 arrest; and increased cell apoptosis in C33A and SiHa cells through Wnt/β-catenin signaling regulation. However, the upregulation of PRAME exhibited the opposite effects accordingly, which could be partly reversed via MSAB treatment. The growth rate of xenograft tumors was enhanced when PRAME was overexpressed via Wnt/β-catenin signaling activation. Taken together, PRAME is associated with cervical cancer occurrence and progression mediated by Wnt/β-catenin signaling, suggesting that PRAME might be a factor in manipulating cervical carcinogenesis and a potential therapeutic target.

摘要

宫颈癌给女性的生活带来了沉重负担,目前它是女性癌症死亡的主要原因。黑色素瘤优先表达抗原(PRAME)属于癌症-睾丸抗原(CTA)基因家族,在不同类型的癌症中被发现异常表达。我们之前的研究也表明,与正常组织相比,PRAME在宫颈癌中高表达。然而,PRAME在宫颈癌中的作用和详细机制尚未得到探索。在本研究中,通过免疫组织化学(IHC)、qRT-PCR和蛋白质免疫印迹法检测了PRAME在宫颈组织和细胞中的表达。此外,进行了CCK-8、BrdU、划痕、Transwell和流式细胞术检测,以探讨PRAME在调节宫颈癌细胞恶性生物学行为中的作用。使用裸鼠在体内证实PRAME在肿瘤生长中的作用。此外,使用Wnt抑制剂MSAB在体外和体内验证PRAME在调节Wnt/β-连环蛋白信号通路中的作用。IHC、qRT-PCR和蛋白质免疫印迹法的结果表明,PRAME在宫颈癌组织和细胞中高表达。通过Wnt/β-连环蛋白信号调节,PRAME基因敲低减弱了C33A和SiHa细胞的生长、迁移和侵袭;诱导G0/G1期阻滞;并增加了细胞凋亡。然而,PRAME的上调相应地表现出相反的效果,通过MSAB处理可部分逆转。当通过Wnt/β-连环蛋白信号激活使PRAME过表达时,异种移植肿瘤的生长速率加快。综上所述,PRAME与Wnt/β-连环蛋白信号介导的宫颈癌发生和进展相关,表明PRAME可能是操纵宫颈癌发生的一个因素和潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d49e/10046627/6b0e3220f35d/cancers-15-01801-g001.jpg

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