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FTO 通过诱导 PIK3R3 mRNA 的 m6A 去甲基化促进宫颈癌恶性进展。

FTO Facilitates Cervical Cancer Malignancy Through Inducing m6A-Demethylation of PIK3R3 mRNA.

作者信息

Chen Bingxin, Wang Liming, Li Xiaomin, Ren Ci, Gao Chun, Ding Wencheng, Wang Hui

机构信息

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Cancer Med. 2024 Dec;13(24):e70507. doi: 10.1002/cam4.70507.

DOI:10.1002/cam4.70507
PMID:39692250
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11653219/
Abstract

BACKGROUND

The incidence rate and mortality of cervical cancer rank the fourth in the global female cancer. N6-methyladenosine (m6A) always plays an important role in tumor progression, and fat mass and obesity-associated gene (FTO) works as the m6A demethylase.

AIMS

Our study aimed to narrate the biological function and potential mechanisms for FTO in cervical cancer malignancy.

MATERIALS & METHODS: We analyzed potential clinical value of FTO in cervical cancer patients. The relative protein levels of FTO in cervical cancerous tissue and paracancerous tissue were verified by IHC. After changing the FTO expression level by lentivirus transfection, the proliferation and metastasis ability of cervical cancer cells were detected both in vitro and in vivo. Further, Merip-seq and Merip-qPCR are used to profile m6A transcriptome-wide. Finally, western blot were performed to identify the regulatory mechanism.

RESULTS

Based on TCGA-CESC cohort and GEO dataset, FTO expression levels in HPV-positive cancer patients were significantly higher than those in HPV-negative cancer patients and could predict advanced FIGO stage. The protein level of FTO in cervical cancerous tissue was higher than that in paracancerous tissue. Functional assays indicated that FTO promoted the proliferation, migration and invasion of cervical cancer cells both in vitro and in vivo. The Merip-seq and Merip-qPCR evoked that relative PIK3R3 m6A level was significantly increased after FTO knockdown, which effected the activation of FoxO pathway. After knocking down FTO, upregulation of PIK3R3 can restore the malignancy of cervical cancer.

CONCLUSION

All in all, these data suggest a vital role for FTO in occurrence and development of cervical cancer.

摘要

背景

宫颈癌的发病率和死亡率在全球女性癌症中排名第四。N6-甲基腺苷（m6A）在肿瘤进展中一直发挥着重要作用，而脂肪量与肥胖相关基因（FTO）作为m6A去甲基化酶。

目的

我们的研究旨在阐述FTO在宫颈癌恶性肿瘤中的生物学功能及潜在机制。

材料与方法

我们分析了FTO在宫颈癌患者中的潜在临床价值。通过免疫组化验证宫颈癌组织和癌旁组织中FTO的相对蛋白水平。经慢病毒转染改变FTO表达水平后，在体外和体内检测宫颈癌细胞的增殖和转移能力。此外，采用甲基化RNA免疫沉淀测序（MeRIP-seq）和甲基化RNA免疫沉淀定量PCR（MeRIP-qPCR）对m6A转录组进行分析。最后，进行蛋白质免疫印迹法以确定调控机制。

结果

基于TCGA-CESC队列和GEO数据集，HPV阳性癌症患者中FTO的表达水平显著高于HPV阴性癌症患者，并且可以预测国际妇产科联盟（FIGO）晚期。宫颈癌组织中FTO的蛋白水平高于癌旁组织。功能试验表明，FTO在体外和体内均促进宫颈癌细胞的增殖、迁移和侵袭。MeRIP-seq和MeRIP-qPCR结果显示，敲低FTO后，PIK3R3的相对m6A水平显著升高，这影响了FoxO通路的激活。敲低FTO后，PIK3R3的上调可恢复宫颈癌的恶性程度。

结论

总而言之，这些数据表明FTO在宫颈癌的发生发展中起着至关重要的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/18881bfcd55c/CAM4-13-e70507-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/d91dc2725601/CAM4-13-e70507-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/a08177d9a2ec/CAM4-13-e70507-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/ed463b833c73/CAM4-13-e70507-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/65b356abdad6/CAM4-13-e70507-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/67d4f95edae2/CAM4-13-e70507-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/dcc9fab73298/CAM4-13-e70507-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/fe69b0e0be6d/CAM4-13-e70507-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/1087ba04ced9/CAM4-13-e70507-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/18881bfcd55c/CAM4-13-e70507-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/d91dc2725601/CAM4-13-e70507-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/a08177d9a2ec/CAM4-13-e70507-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/ed463b833c73/CAM4-13-e70507-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/65b356abdad6/CAM4-13-e70507-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/67d4f95edae2/CAM4-13-e70507-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/dcc9fab73298/CAM4-13-e70507-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/fe69b0e0be6d/CAM4-13-e70507-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/1087ba04ced9/CAM4-13-e70507-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cb/11653219/18881bfcd55c/CAM4-13-e70507-g002.jpg

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J Transl Med. 2024 May 10;22(1):442. doi: 10.1186/s12967-024-05242-3.
2
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Trends Genet. 2024 Feb;40(2):160-174. doi: 10.1016/j.tig.2023.11.003. Epub 2024 Jan 12.
3
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4
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7
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