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环状 RNA_0067717 通过作为 TRIM41 和 p53 的支架促进鼻咽癌对紫杉醇的耐药性。

circRNA_0067717 promotes paclitaxel resistance in nasopharyngeal carcinoma by acting as a scaffold for TRIM41 and p53.

机构信息

Department of Oncology, Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410013, China.

出版信息

Cell Oncol (Dordr). 2023 Jun;46(3):677-695. doi: 10.1007/s13402-023-00776-y. Epub 2023 Jan 27.


DOI:10.1007/s13402-023-00776-y
PMID:36705889
Abstract

PURPOSE: Circular RNAs (circRNAs) play important roles in tumour progression. This study aimed to explore the mechanism of hsa_circ_0067717 (termed circRNA_0067717) promoting paclitaxel resistance in nasopharyngeal carcinoma (NPC). METHODS: We assayed CNE-1 and HNE-2 parental cell lines and the corresponding paclitaxel-resistant NPC cell lines using circRNA microarrays. RNA pull-down assay, RNA immunoprecipitation, and RNA fluorescence in situ hybridization were used to identify the molecular mechanisms. RESULTS: Here, we confirm that circRNA_0067717 is significantly upregulated in NPC paclitaxel-resistant cells and is associated with paclitaxel resistance in NPC. Mechanistically, circRNA_0067717 functions as a scaffold for TRIM41 protein (a ubiquitin E3 ligase) and p53 protein. In nasopharyngeal carcinoma paclitaxel-resistant cells, the highly expressed circRNA_0067717 can bind to more TRIM41 and p53 protein, promoting TRIM41-induced p53 ubiquitination and degradation, resulting in a decrease in p53 protein level. Moreover, the 1-176 nt area of circRNA_0067717 and the 301-425 nt region of circRNA_0067717 are the binding sites for p53 and TRIM41, respectively. The resistance of NPC cells to paclitaxel can be reduced by blocking these binding regions of circRNA_0067717. CONCLUSION: We demonstrate that circRNA_0067717 acts as a scaffold for TRIM41 and p53, enhancing paclitaxel chemoresistance in NPC by promoting TRIM41-induced p53 degradation via ubiquitination.

摘要

目的:环状 RNA(circRNAs)在肿瘤进展中发挥重要作用。本研究旨在探讨 hsa_circ_0067717(称为 circRNA_0067717)促进鼻咽癌(NPC)紫杉醇耐药的机制。

方法:我们使用 circRNA 微阵列检测 CNE-1 和 HNE-2 亲本细胞系和相应的紫杉醇耐药 NPC 细胞系。采用 RNA 下拉实验、RNA 免疫沉淀和 RNA 荧光原位杂交来鉴定分子机制。

结果:在这里,我们证实 circRNA_0067717 在 NPC 紫杉醇耐药细胞中显著上调,并与 NPC 中的紫杉醇耐药相关。在机制上,circRNA_0067717 作为 TRIM41 蛋白(一种泛素 E3 连接酶)和 p53 蛋白的支架。在鼻咽癌紫杉醇耐药细胞中,高表达的 circRNA_0067717 可以与更多的 TRIM41 和 p53 蛋白结合,促进 TRIM41 诱导的 p53 泛素化和降解,导致 p53 蛋白水平降低。此外,circRNA_0067717 的 1-176nt 区域和 circRNA_0067717 的 301-425nt 区域分别是 p53 和 TRIM41 的结合位点。通过阻断 circRNA_0067717 的这些结合区域,可以降低 NPC 细胞对紫杉醇的耐药性。

结论:我们证明 circRNA_0067717 作为 TRIM41 和 p53 的支架,通过促进 TRIM41 诱导的 p53 降解来增强 NPC 中的紫杉醇化疗耐药性,从而促进 p53 降解。

相似文献

[1]
circRNA_0067717 promotes paclitaxel resistance in nasopharyngeal carcinoma by acting as a scaffold for TRIM41 and p53.

Cell Oncol (Dordr). 2023-6

[2]
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Braz J Otorhinolaryngol. 2024

[3]
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Mol Cancer. 2021-8-31

[4]
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Int J Med Sci. 2020

[5]
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Mol Cancer. 2022-10-5

[6]
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Eur Rev Med Pharmacol Sci. 2019-4

[7]
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[8]
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Aging (Albany NY). 2020-10-20

[9]
Identification of differentially expressed circular RNAs in human nasopharyngeal carcinoma.

Cancer Biomark. 2020

[10]
Circular RNA ITCH attenuates the progression of nasopharyngeal carcinoma by inducing PTEN upregulation via miR-214.

J Gene Med. 2022-1

引用本文的文献

[1]
Circular RNAs: key regulators of paclitaxel sensitivity and resistance in cancer.

Eur J Med Res. 2025-8-18

[2]
Circular RNAs in cancer.

MedComm (2020). 2025-2-2

[3]
CircKRT75 augments the cisplatin chemoresistance of nasopharyngeal carcinoma via targeting miR-659/CCAR2 axis.

J Mol Histol. 2024-11-29

[4]
Research progress on the role and mechanism of circular RNA in drug resistance of head and neck squamous cell carcinoma.

Cancer Drug Resist. 2024-9-2

[5]
Predicting the potential associations between circRNA and drug sensitivity using a multisource feature-based approach.

J Cell Mol Med. 2024-10

[6]
Roles and mechanisms of circular RNA in respiratory system cancers.

Front Oncol. 2024-7-15

[7]
Emerging roles of circular RNAs in nasopharyngeal carcinoma: functions and implications.

Cell Death Discov. 2024-4-25

[8]
Circular RNAs in gynecologic cancers: mechanisms and implications for chemotherapy resistance.

Front Pharmacol. 2023-6-8

本文引用的文献

[1]
CircOGDH Is a Penumbra Biomarker and Therapeutic Target in Acute Ischemic Stroke.

Circ Res. 2022-3-18

[2]
Circular RNA ANAPC7 Inhibits Tumor Growth and Muscle Wasting via PHLPP2-AKT-TGF-β Signaling Axis in Pancreatic Cancer.

Gastroenterology. 2022-6

[3]
METTL14-mediated mA modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis.

Mol Cancer. 2022-2-14

[4]
Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity.

Mol Cell. 2022-1-6

[5]
Circular RNA ACTN4 promotes intrahepatic cholangiocarcinoma progression by recruiting YBX1 to initiate FZD7 transcription.

J Hepatol. 2022-1

[6]
Circ-GALNT16 restrains colorectal cancer progression by enhancing the SUMOylation of hnRNPK.

J Exp Clin Cancer Res. 2021-8-27

[7]
FUS-induced circRHOBTB3 facilitates cell proliferation via miR-600/NACC1 mediated autophagy response in pancreatic ductal adenocarcinoma.

J Exp Clin Cancer Res. 2021-8-20

[8]
CircSLC7A2 protects against osteoarthritis through inhibition of the miR-4498/TIMP3 axis.

Cell Prolif. 2021-6

[9]
p53 and Tumor Suppression: It Takes a Network.

Trends Cell Biol. 2021-4

[10]
Circ_SMAD4 promotes gastric carcinogenesis by activating wnt/β-catenin pathway.

Cell Prolif. 2021-3

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