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mC 修饰介导的 mRNA 稳定性上调 LRRC8A 抑制宫颈癌细胞凋亡并促进肿瘤发生。

Upregulation of LRRC8A by mC modification-mediated mRNA stability suppresses apoptosis and facilitates tumorigenesis in cervical cancer.

机构信息

Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China.

Department of Obstetrics and Gynecology, Daping Hospital, Army Medical University, Chongqing 400042, China.

出版信息

Int J Biol Sci. 2023 Jan 1;19(2):691-704. doi: 10.7150/ijbs.79205. eCollection 2023.

DOI:10.7150/ijbs.79205
PMID:36632452
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9830503/
Abstract

Cervical cancer (CC) is one of the most common gynecological malignancies with poor prognosis for advanced CC patients. LRRC8A is a volume-regulated anion channel protein involved in cellular homeostasis, but its role in CC remains largely unknown. In this study, we found that LRRC8A is elevated in CC and associated with poor prognosis. LRRC8A maintains cell survivals under the hypotonic condition, and promotes tumorigenesis through apoptosis suppression and . Notably, LRRC8A is upregulated by NSUN2-mediated mC modification. mC modified-LRRC8A mRNA is bound by the RNA binding protein YBX1 followed by the increased RNA stability. Moreover, loss of NSUN2 suppresses the proliferation and metastasis of CC cells, and NSUN2 expression is positively correlated with LRRC8A expression in CC. Altogether, our study demonstrates that the NSUN2-mC-LRRC8A axis is crucial and would be a potential therapeutic target for CC.

摘要

宫颈癌（CC）是最常见的妇科恶性肿瘤之一，晚期 CC 患者的预后较差。LRRC8A 是一种参与细胞内稳态的容积调节阴离子通道蛋白，但它在 CC 中的作用在很大程度上尚不清楚。在本研究中，我们发现 LRRC8A 在 CC 中上调，并与预后不良相关。LRRC8A 在低渗条件下维持细胞存活，并通过抑制细胞凋亡和促进肿瘤发生。值得注意的是，LRRC8A 是由 NSUN2 介导的 mC 修饰上调的。mC 修饰的 LRRC8A mRNA 与 RNA 结合蛋白 YBX1 结合，随后 RNA 稳定性增加。此外，NSUN2 的缺失抑制了 CC 细胞的增殖和转移，并且 CC 中 NSUN2 的表达与 LRRC8A 的表达呈正相关。总之，我们的研究表明，NSUN2-mC-LRRC8A 轴至关重要，可能成为 CC 的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/9830503/94d911976462/ijbsv19p0691g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/9830503/1af7491338bd/ijbsv19p0691g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/9830503/db10c3dc5dff/ijbsv19p0691g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/9830503/882463225775/ijbsv19p0691g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/9830503/eb6d5228f4e5/ijbsv19p0691g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/9830503/e4198cc7b8e6/ijbsv19p0691g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/9830503/5fcb75500129/ijbsv19p0691g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/9830503/94d911976462/ijbsv19p0691g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/9830503/1af7491338bd/ijbsv19p0691g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/9830503/b6cc3a0e5e84/ijbsv19p0691g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/9830503/db10c3dc5dff/ijbsv19p0691g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/9830503/882463225775/ijbsv19p0691g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/9830503/eb6d5228f4e5/ijbsv19p0691g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/9830503/e4198cc7b8e6/ijbsv19p0691g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/9830503/5fcb75500129/ijbsv19p0691g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/9830503/94d911976462/ijbsv19p0691g008.jpg

相似文献

[1]
Upregulation of LRRC8A by mC modification-mediated mRNA stability suppresses apoptosis and facilitates tumorigenesis in cervical cancer.

Int J Biol Sci. 2023

[2]
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[4]
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[5]
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[6]
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[7]
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[8]
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引用本文的文献

[1]
Epitranscriptomic mechanisms and implications of RNA mC modification in cancer.

Theranostics. 2025-7-25

[2]
Ethyl β-carboline-3-carboxylate targets PRDX5/c-Jun axis for novel therapeutic strategy against cervical cancer.

Discov Oncol. 2025-8-7

[3]
NSUN2-mediated RNA mC modification drives multiple myeloma progression by enhancing the stability of HIP1 mRNA.

Sci Rep. 2025-7-31

[4]
Research on RNA modification in disease diagnosis and prognostic biomarkers: current status and challenges.

Brief Bioinform. 2025-7-2

[5]
NSUN2-mediated cytosine-5 methylation of FSP1 protects acute myeloid leukemia cells from ferroptosis.

Mol Cancer. 2025-7-21

[6]
NSUN2 knockdown ameliorates hepatic glucose and lipid metabolism disorders in type 2 diabetes mellitus through the Inhibition of ACSL6 m5C methylation.

Lipids Health Dis. 2025-7-10

[7]
LRRC8A/PKC/FLNA pathway activation is detrimental to colon cancer patients.

Funct Integr Genomics. 2025-6-27

[8]
2'-O-methylation and N6-methyladenosine enhance the oral delivery of small RNAs in mice.

Mol Ther Nucleic Acids. 2025-5-24

[9]
Oral ENPP1 inhibitor designed using generative AI as next generation STING modulator for solid tumors.

Nat Commun. 2025-5-23

[10]
Development of a reliable risk prognostic model for lung adenocarcinoma based on the genes related to endotheliocyte senescence.

Sci Rep. 2025-4-12

本文引用的文献

[1]
Integrative Analyses of m6A Regulators Identify that METTL3 is Associated with HPV Status and Immunosuppressive Microenvironment in HPV-related Cancers.

Int J Biol Sci. 2022

[2]
Why US Cervical Cancer Survival Rates Haven't Improved for Decades.

JAMA. 2022-5-24

[3]
MODOMICS: a database of RNA modification pathways. 2021 update.

Nucleic Acids Res. 2022-1-7

[4]
mRNA m5C controls adipogenesis by promoting CDKN1A mRNA export and translation.

RNA Biol. 2021-11-12

[5]
NSUN2-mediated RNA 5-methylcytosine promotes esophageal squamous cell carcinoma progression via LIN28B-dependent GRB2 mRNA stabilization.

Oncogene. 2021-9

[6]
Acid-base transporters and pH dynamics in human breast carcinomas predict proliferative activity, metastasis, and survival.

Elife. 2021-7-5

[7]
Zinc transporter SLC39A13/ZIP13 facilitates the metastasis of human ovarian cancer cells via activating Src/FAK signaling pathway.

J Exp Clin Cancer Res. 2021-6-21

[8]
LRRC8A influences the growth of gastric cancer cells via the p53 signaling pathway.

Gastric Cancer. 2021-9

[9]
PRDM4 inhibits cell proliferation and tumorigenesis by inactivating the PI3K/AKT signaling pathway through targeting of PTEN in cervical carcinoma.

Oncogene. 2021-5

[10]
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.

CA Cancer J Clin. 2021-5

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