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FOXA1 导致 SIX4 异常表达，影响宫颈癌细胞的生长和化疗耐药性。

FOXA1 Leads to Aberrant Expression of SIX4 Affecting Cervical Cancer Cell Growth and Chemoresistance.

机构信息

Department of Radiotherapy, Jilin Cancer Hospital, Changchun, 130000 Jilin, China.

Department of Oncology, Jilin Cancer Hospital, Changchun, 130000 Jilin, China.

出版信息

Anal Cell Pathol (Amst). 2022 Apr 20;2022:9675466. doi: 10.1155/2022/9675466. eCollection 2022.

DOI:10.1155/2022/9675466
PMID:35498155
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9045987/
Abstract

Cervical cancer (CC) is among the most prevalent cancers among female populations with high recurrence rates all over the world. Cisplatin (DDP) is the first-line treatment for multiple cancers, including CC. The main problem associated with its clinical application is drug resistance. This study is aimed at investigating the function and downstream regulation mechanism of forkhead-box A1 (FOXA1) in CC, which was verified as an oncogene in several cancers. Using GEO database and bioinformatics analysis, we identified FOXA1 as a possible oncogene in CC. Silencing of FOXA1 inhibited CC cell growth, invasion, and chemoresistance. Afterwards, the downstream gene of FOXA1 was predicted using a bioinformatics website and validated using ChIP and dual-luciferase assays. SIX4, a possible target of FOXA1, promoted CC cell malignant aggressiveness and chemoresistance. In addition, overexpression of SIX4 promoted phosphorylation of PI3K and AKT proteins and activated the PI3K/AKT signaling pathway. Further overexpression of SIX4 reversed the repressive effects of FOXA1 knockdown on CC cell growth, invasion, and chemoresistance in DDP-resistant cells. FOXA1-induced SIX4 facilitates CC progression and chemoresistance, highlighting a strong potential for FOXA1 to serve as a promising therapeutic target in CC.

摘要

宫颈癌（CC）是女性人群中最常见的癌症之一，在全球范围内复发率很高。顺铂（DDP）是多种癌症的一线治疗药物，包括 CC。其临床应用的主要问题是耐药性。本研究旨在研究叉头框蛋白 A1（FOXA1）在 CC 中的功能及其下游调控机制，FOXA1 在几种癌症中被证实为致癌基因。通过 GEO 数据库和生物信息学分析，我们确定 FOXA1 是 CC 中的一个可能的致癌基因。沉默 FOXA1 抑制 CC 细胞的生长、侵袭和化疗耐药性。随后，使用生物信息学网站预测 FOXA1 的下游基因，并通过 ChIP 和双荧光素酶测定进行验证。SIX4 是 FOXA1 的一个可能的靶基因，促进了 CC 细胞的恶性侵袭和化疗耐药性。此外，SIX4 的过表达促进了 PI3K 和 AKT 蛋白的磷酸化，并激活了 PI3K/AKT 信号通路。进一步过表达 SIX4 逆转了 FOXA1 敲低对 DDP 耐药细胞中 CC 细胞生长、侵袭和化疗耐药性的抑制作用。FOXA1 诱导的 SIX4 促进了 CC 的进展和化疗耐药性，这突出表明 FOXA1 具有作为 CC 有前途的治疗靶点的强大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46ab/9045987/02507ce22151/ACP2022-9675466.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46ab/9045987/d61d97bb170d/ACP2022-9675466.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46ab/9045987/841f363095f8/ACP2022-9675466.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46ab/9045987/6821260dddbe/ACP2022-9675466.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46ab/9045987/4a4e4934b0c6/ACP2022-9675466.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46ab/9045987/02507ce22151/ACP2022-9675466.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46ab/9045987/d61d97bb170d/ACP2022-9675466.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46ab/9045987/841f363095f8/ACP2022-9675466.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46ab/9045987/6821260dddbe/ACP2022-9675466.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46ab/9045987/4a4e4934b0c6/ACP2022-9675466.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46ab/9045987/02507ce22151/ACP2022-9675466.005.jpg

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本文引用的文献

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Mol Cancer. 2021 May 18;20(1):77. doi: 10.1186/s12943-021-01369-9.
3
LINC00662 modulates cervical cancer cell proliferation, invasion, and apoptosis via sponging miR-103a-3p and upregulating PDK4.LINC00662 通过海绵吸附 miR-103a-3p 并上调 PDK4 来调节宫颈癌细胞的增殖、侵袭和凋亡。
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Cell Death Discov. 2024 Apr 11;10(1):172. doi: 10.1038/s41420-024-01936-1.
4
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Kaohsiung J Med Sci. 2023 Nov;39(11):1077-1086. doi: 10.1002/kjm2.12737. Epub 2023 Sep 2.
Mol Carcinog. 2021 Jun;60(6):365-376. doi: 10.1002/mc.23294. Epub 2021 Apr 5.
4
The Role of microRNAs in the Cisplatin- and Radio-Resistance of Cervical Cancer.微小RNA在宫颈癌顺铂耐药和放疗抵抗中的作用
Cancers (Basel). 2021 Mar 9;13(5):1168. doi: 10.3390/cancers13051168.
5
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6
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