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骨形态发生蛋白抑制剂卵泡抑素样蛋白1(FSTL1)可抑制宫颈癌发生。

The BMP inhibitor follistatin-like 1 (FSTL1) suppresses cervical carcinogenesis.

作者信息

Zhao Chenjing, Chen Zhongjie, Zhu Li, Miao Yunheng, Guo Jiasen, Yuan Zhiyong, Wang Ping, Li Lian, Ning Wen

机构信息

State Key Laboratory of Medical Chemical Biology, Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Nankai University, Tianjin, China.

Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

出版信息

Front Oncol. 2023 Jan 23;13:1100045. doi: 10.3389/fonc.2023.1100045. eCollection 2023.

Abstract

Follistatin-like 1 (FSTL1) is a cancer-related matricellular secretory protein with contradictory organ-specific roles. Its contribution to the pathogenesis of cervical carcinoma is still not clear. Meanwhile, it is necessary to identify novel candidate genes to understand cervical carcinoma's pathogenesis further and find potential therapeutic targets. We collected cervical carcinoma samples and matched adjacent tissues from patients with the locally-advanced disease and used cervical carcinoma cell lines HeLa and C33A to evaluate the effects of FSTL1 on CC cells. The mRNA transcription and protein expression of FSTL1 in cervical carcinoma tumor biopsy tissues were lower than those of matched adjacent tissues. Patients with a lower ratio of mRNA between the tumor and its matched adjacent tissues showed a correlation with the advanced cervical carcinoma FIGO stages. High expression of FSTL1 markedly inhibited the proliferation, motility, and invasion of HeLa and C33A. Regarding mechanism, FSTL1 plays its role by negatively regulating the BMP4/Smad1/5/9 signaling. Our study has demonstrated the tumor suppressor effect of FSTL1, and these findings suggested a potential therapeutic target and biomarker for cervical carcinoma.

摘要

卵泡抑素样蛋白1(FSTL1)是一种与癌症相关的基质细胞分泌蛋白,在不同器官中发挥着相互矛盾的作用。其在宫颈癌发病机制中的作用尚不清楚。同时,有必要鉴定新的候选基因,以进一步了解宫颈癌的发病机制并寻找潜在的治疗靶点。我们收集了局部晚期宫颈癌患者的癌组织样本及其配对的相邻组织,并使用宫颈癌细胞系HeLa和C33A来评估FSTL1对宫颈癌细胞的影响。FSTL1在宫颈癌肿瘤活检组织中的mRNA转录和蛋白表达低于其配对的相邻组织。肿瘤与其配对的相邻组织之间mRNA比值较低的患者与晚期宫颈癌国际妇产科联盟(FIGO)分期相关。FSTL1的高表达显著抑制了HeLa和C33A细胞的增殖、迁移和侵袭。在机制方面,FSTL1通过负调控BMP4/Smad1/5/9信号通路发挥作用。我们的研究证明了FSTL1的肿瘤抑制作用,这些发现提示其可能成为宫颈癌的治疗靶点和生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f934/9901576/cd6d5e36bbd8/fonc-13-1100045-g001.jpg

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