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基于长链非编码RNA的功能预测揭示了Notch上调型卵巢癌中的新靶点。

Long Non-Coding RNA-Based Functional Prediction Reveals Novel Targets in Notch-Upregulated Ovarian Cancer.

作者信息

Jeong Seonhyang, Park Sunmi, Jo Young Suk, Choi Moon Jung, Lee Gibbeum, Lee Seul Gi, Choi Min Chul, Park Hyun, Joo Won Duk, Jung Sang Geun, Lee Jandee

机构信息

Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.

Department of Surgery, Open NBI Convergence Technology Research Laboratory, Severance Hospital, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.

出版信息

Cancers (Basel). 2022 Mar 18;14(6):1557. doi: 10.3390/cancers14061557.

DOI:10.3390/cancers14061557
PMID:35326706
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8946805/
Abstract

Notch signaling is a druggable target in high-grade serous ovarian cancers; however, its complexity is not clearly understood. Recent revelations of the biological roles of lncRNAs have led to an increased interest in the oncogenic action of lncRNAs in various cancers. In this study, we performed in silico analyses using The Cancer Genome Atlas data to discover novel Notch-related lncRNAs and validated our transcriptome data via NOTCH1/3 silencing in serous ovarian cancer cells. The expression of novel Notch-related lncRNAs was down-regulated by a Notch inhibitor and was upregulated in high-grade serous ovarian cancers, compared to benign or borderline ovarian tumors. Functionally, Notch-related lncRNAs were tightly linked to Notch-related changes in diverse gene expressions. Notably, genes related to DNA repair and spermatogenesis showed specific correlations with Notch-related lncRNAs. Master transcription factors, including EGR1, CTCF, GABPα, and E2F4 might orchestrate the upregulation of Notch-related lncRNAs, along with the associated genes. The discovery of Notch-related lncRNAs significantly contributes to our understanding of the complex crosstalk of Notch signaling with other oncogenic pathways at the transcriptional level.

摘要

Notch信号通路是高级别浆液性卵巢癌中的一个可成药靶点；然而，其复杂性尚未得到清晰的理解。lncRNAs生物学作用的最新揭示引发了人们对lncRNAs在各种癌症中致癌作用的更多关注。在本研究中，我们使用癌症基因组图谱数据进行了计算机分析，以发现新的Notch相关lncRNAs，并通过在浆液性卵巢癌细胞中沉默NOTCH1/3来验证我们的转录组数据。与良性或交界性卵巢肿瘤相比，新型Notch相关lncRNAs的表达在Notch抑制剂作用下下调，在高级别浆液性卵巢癌中上调。在功能上，Notch相关lncRNAs与多种基因表达中Notch相关的变化紧密相关。值得注意的是，与DNA修复和精子发生相关的基因与Notch相关lncRNAs表现出特定的相关性。包括EGR1、CTCF、GABPα和E2F4在内的主转录因子可能协同调控Notch相关lncRNAs及其相关基因的上调。Notch相关lncRNAs的发现显著有助于我们在转录水平上理解Notch信号通路与其他致癌途径的复杂相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/8946805/801e39aacced/cancers-14-01557-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/8946805/4455ec7fd8a2/cancers-14-01557-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/8946805/09bed9a66f52/cancers-14-01557-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/8946805/59028deb5435/cancers-14-01557-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/8946805/332c38c7fdba/cancers-14-01557-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/8946805/801e39aacced/cancers-14-01557-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/8946805/4455ec7fd8a2/cancers-14-01557-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/8946805/09bed9a66f52/cancers-14-01557-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/8946805/59028deb5435/cancers-14-01557-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/8946805/332c38c7fdba/cancers-14-01557-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05dc/8946805/801e39aacced/cancers-14-01557-g005.jpg

相似文献

[1]
Long Non-Coding RNA-Based Functional Prediction Reveals Novel Targets in Notch-Upregulated Ovarian Cancer.

Cancers (Basel). 2022-3-18

[2]
Crosstalk between the Notch signaling pathway and long non-coding RNAs.

Cancer Lett. 2018-2-2

[3]
RNA profiling of human testicular cells identifies syntenic lncRNAs associated with spermatogenesis.

Hum Reprod. 2019-7-8

[4]
Comprehensive analysis of long non-coding RNAs in ovarian cancer reveals global patterns and targeted DNA amplification.

PLoS One. 2013-11-12

[5]
A computational guided, functional validation of a novel therapeutic antibody proposes Notch signaling as a clinical relevant and druggable target in glioma.

Sci Rep. 2020-10-1

[6]
Long Non-Coding RNA HAND2-AS1 Acts as a Tumor Suppressor in High-Grade Serous Ovarian Carcinoma.

Int J Mol Sci. 2020-6-5

[7]
Systematic analysis reveals a lncRNA-mRNA co-expression network associated with platinum resistance in high-grade serous ovarian cancer.

Invest New Drugs. 2017-10-30

[8]
Notch-associated lncRNAs profiling circuiting epigenetic modification in colorectal cancer.

Cancer Cell Int. 2022-10-13

[9]
miR-223 potentially targets SWI/SNF complex protein SMARCD1 in atypical proliferative serous tumor and high-grade ovarian serous carcinoma.

Hum Pathol. 2017-10-24

[10]
Gene microarray analysis of lncRNA and mRNA expression profiles in patients with high‑grade ovarian serous cancer.

Int J Mol Med. 2018-3-23

引用本文的文献

[1]
Aggressive serous ovarian cancer subtype defined by high centrality lncRNA profiles and master transcription factors.

Sci Rep. 2025-7-1

[2]
NONHSAT098487.2 protects cardiomyocytes from oxidative stress injury by regulating the Notch pathway.

Heliyon. 2023-6-21

[3]
Comparative analysis between highgrade serous ovarian cancer and healthy ovarian tissues using single-cell RNA sequencing.

Front Oncol. 2023-4-14

本文引用的文献

[1]
Simultaneous Expression of Long Non-Coding RNA and Extracellular Matrix Protein 1 Defines Tumour Behaviour in Young Patients with Papillary Thyroid Cancer.

Cancers (Basel). 2021-6-28

[2]
LncRNA HOTAIR regulates anoikis-resistance capacity and spheroid formation of ovarian cancer cells by recruiting EZH2 and influencing H3K27 methylation.

Neoplasma. 2021-5

[3]
The role of neoadjuvant chemotherapy in the management of low-grade serous carcinoma of the ovary and peritoneum: Further evidence of relative chemoresistance.

Gynecol Oncol. 2020-9

[4]
The Novel Notch-induced Long Noncoding RNA LUNAR1 Determines the Proliferation and Prognosis of Colorectal Cancer.

Sci Rep. 2019-12-27

[5]
Global patterns and trends in ovarian cancer incidence: age, period and birth cohort analysis.

BMC Cancer. 2019-10-22

[6]
The use of cisplatin plus doxorubicin or paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) for stage IIIC or IV epithelial ovarian cancer: a comparative study.

Clin Transl Oncol. 2019-2-20

[7]
Computational models for lncRNA function prediction and functional similarity calculation.

Brief Funct Genomics. 2019-2-14

[8]
Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers.

Endocr Relat Cancer. 2018-2-12

[9]
Genetic epidemiology of ovarian cancer and prospects for polygenic risk prediction.

Gynecol Oncol. 2017-12

[10]
Notch inhibitors and their role in the treatment of triple negative breast cancer: promises and failures.

Curr Opin Oncol. 2017-11

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