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METTL3 介导的长非编码 RNA RHPN1-AS1 的 m6A 修饰通过激活 PI3K/AKT 通路增强卵巢癌细胞对顺铂的耐药性。

METTL3-mediated m6A modification of lnc RNA RHPN1-AS1 enhances cisplatin resistance in ovarian cancer by activating PI3K/AKT pathway.

机构信息

Department of Gynaecology and Obstetrics, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China.

出版信息

J Clin Lab Anal. 2022 Dec;36(12):e24761. doi: 10.1002/jcla.24761. Epub 2022 Nov 6.

DOI:10.1002/jcla.24761
PMID:36336887
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9756993/
Abstract

BACKGROUND

Cisplatin resistance is a big challenge for ovarian cancer (OC) therapy. The abnormal expression of long noncoding RNAs (lncRNAs) regulated by N6-methyladenosine (m6A) modification has been confirmed to play the crucial roles in OC. The aim of this study is to explore the regulatory mechanism of lncRNA RHPN1-AS1 on OC with cisplatin resistance.

METHODS

The real-time reverse transcription-polymerase chain reaction was carried out to confirm the expression of RHPN1-AS1 and methyltransferase-like 3 (METTL3) in OC. The effects of RHPN1-AS1 on cisplatin-resistant OC cells were identified by cell functional experiments and animal experiment. Western blotting was performed to detect the effect of RHPN1-AS1 on PI3K/AKT pathway. Moreover, methylated RNA immunoprecipitation and RNA stability assays confirmed the interaction between RHPN1-AS1 and METTL3.

RESULTS

RHPN1-AS1 and METTL3 were confirmed to be overexpressed in OC. After transfecting RHPN1-AS1 overexpression or RHPN1-AS1 knockdown vectors into cisplatin-resistant OC cells, it was found that upregulating RHPN1-AS1 contributed to cell viability, migration, invasion, and tumor growth in vivo. In addition, RHPN1-AS1 could enhance the protein levels of PI3K and phosphorylated AKT in cisplatin-resistant OC cells, and METTL3 could enhance the stability of RHPN1-AS1 by the m6A modification.

CONCLUSION

Overall, this study revealed that METTL3-mediated m6A modification of RHPN1-AS1 accelerates cisplatin resistance in OC by activating PI3K/AKT pathway.

摘要

背景

顺铂耐药是卵巢癌（OC）治疗的一大挑战。现已证实，受 N6-甲基腺苷（m6A）修饰调控的长链非编码 RNA（lncRNA）的异常表达在 OC 中发挥着关键作用。本研究旨在探讨 lncRNA RHPN1-AS1 对顺铂耐药 OC 的调控机制。

方法

采用实时逆转录-聚合酶链反应（qRT-PCR）检测 OC 中 RHPN1-AS1 和甲基转移酶样 3（METTL3）的表达。通过细胞功能实验和动物实验鉴定 RHPN1-AS1 对顺铂耐药 OC 细胞的影响。Western blot 检测 RHPN1-AS1 对 PI3K/AKT 通路的影响。此外，采用甲基化 RNA 免疫沉淀（MeRIP）和 RNA 稳定性测定实验证实 RHPN1-AS1 与 METTL3 之间的相互作用。

结果

RHPN1-AS1 和 METTL3 在 OC 中呈过表达。将 RHPN1-AS1 过表达或敲低载体转染至顺铂耐药 OC 细胞后，发现上调 RHPN1-AS1 可促进顺铂耐药 OC 细胞的活力、迁移和侵袭以及体内肿瘤生长。此外，RHPN1-AS1 可增强顺铂耐药 OC 细胞中 PI3K 和磷酸化 AKT 的蛋白水平，METTL3 可通过 m6A 修饰增强 RHPN1-AS1 的稳定性。

结论

综上所述，本研究表明，METTL3 介导的 RHPN1-AS1 的 m6A 修饰通过激活 PI3K/AKT 通路加速 OC 中的顺铂耐药。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2da/9756993/90715fe491f1/JCLA-36-e24761-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2da/9756993/4e0a703c81e5/JCLA-36-e24761-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2da/9756993/7cd7989673d4/JCLA-36-e24761-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2da/9756993/de76e3edb158/JCLA-36-e24761-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2da/9756993/7200e4ffc8c6/JCLA-36-e24761-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2da/9756993/f78ac9aeceb8/JCLA-36-e24761-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2da/9756993/90715fe491f1/JCLA-36-e24761-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2da/9756993/4e0a703c81e5/JCLA-36-e24761-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2da/9756993/e4fc5a20145c/JCLA-36-e24761-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2da/9756993/7cd7989673d4/JCLA-36-e24761-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2da/9756993/de76e3edb158/JCLA-36-e24761-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2da/9756993/f78ac9aeceb8/JCLA-36-e24761-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2da/9756993/90715fe491f1/JCLA-36-e24761-g006.jpg

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3
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4
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Mol Ther Oncolytics. 2021 Jul 21;22:574-581. doi: 10.1016/j.omto.2021.07.004. eCollection 2021 Sep 24.
5
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6
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