LURAP1L-AS1 long noncoding RNA promotes breast cancer progression and associates with poor prognosis

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research Pub Date : 2025-01-19 DOI:10.1016/j.ncrna.2025.01.006

Radhakrishnan Vishnubalaji , Dania Awata , Nehad M. Alajez

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Abstract

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of cancer biology, yet their roles in breast cancer, particularly in triple-negative breast cancer (TNBC), remain incompletely understood. Through a custom siRNA library screen targeting TNBC-associated lncRNAs in MDA-MB-231 and BT-549 TNBC cell models, we identified LURAP1L-AS1 as a key modulator of TNBC progression. Survival analysis of TNBC patients demonstrated a significant association between elevated LURAP1L-AS1 expression and poor clinical outcomes.

LURAP1L-AS1 knockdown significantly impaired colony formation and organoid growth of TNBC models, associated with increased apoptosis thus highlighting its role in promoting tumorigenicity. RNA sequencing of LURAP1L-AS1-depleted cells revealed dysregulation of pathways related to cell proliferation, apoptosis, migration, and RNA processing. Bioinformatics analysis predicted LURAP1L-AS1 to function as a competitive endogenous RNA (ceRNA), sponging key microRNAs, such as miR-7a-5p, miR-101-3p, miR-181a-5p, and miR-27a-3p, thereby modulating oncogenes including EZH2, MCL1, and KRAS, which are linked to increased cancer cell survival, proliferation, and metastasis.

In addition to its role in TNBC, correlation analysis using breast cancer patient datasets revealed a significant association between LURAP1L-AS1 and ESR1 expression, suggesting its broader impact across breast cancer subtypes. Concordantly, LURAP1L-AS1 depletion inhibited estrogen receptor-positive (ER+) MCF7 breast cancer cells colony formation and organotypic growth.

Our findings establish LURAP1L-AS1 as a functional lncRNA that promotes breast cancer progression, highlighting its potential for use in RNA-based therapies for breast cancer.

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LURAP1L-AS1长链非编码RNA促进乳腺癌进展并与不良预后相关

长链非编码rna （lncRNAs）正在成为癌症生物学的关键调控因子，但它们在乳腺癌，特别是三阴性乳腺癌（TNBC）中的作用仍不完全清楚。通过针对MDA-MB-231和BT-549 TNBC细胞模型中TNBC相关lncrna的定制siRNA文库筛选，我们发现LURAP1L-AS1是TNBC进展的关键调节剂。TNBC患者的生存分析显示，LURAP1L-AS1表达升高与临床预后不良之间存在显著关联。LURAP1L-AS1敲低显著损害TNBC模型的集落形成和类器官生长，与细胞凋亡增加相关，从而突出其促进肿瘤发生的作用。对lurap1l - as1缺失细胞的RNA测序显示，与细胞增殖、凋亡、迁移和RNA加工相关的通路失调。生物信息学分析预测，LURAP1L-AS1作为竞争性内源性RNA （ceRNA）发挥作用，吞噬关键microrna，如miR-7a-5p、miR-101-3p、miR-181a-5p和miR-27a-3p，从而调节癌基因，包括EZH2、MCL1和KRAS，这些癌基因与癌细胞存活、增殖和转移增加有关。除了在TNBC中发挥作用外，使用乳腺癌患者数据集进行的相关分析显示，LURAP1L-AS1和ESR1表达之间存在显著关联，表明其在乳腺癌亚型中具有更广泛的影响。与此同时，LURAP1L-AS1缺失抑制雌激素受体阳性（ER+） MCF7乳腺癌细胞集落形成和器官型生长。我们的研究结果证实了LURAP1L-AS1是一种促进乳腺癌进展的功能性lncRNA，突出了其在基于rna的乳腺癌治疗中的潜力。

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来源期刊

Non-coding RNA Research Medicine-Biochemistry (medical)

CiteScore

7.70

自引率

6.00%

发文量

审稿时长

49 days

期刊介绍： Non-coding RNA Research aims to publish high quality research and review articles on the mechanistic role of non-coding RNAs in all human diseases. This interdisciplinary journal will welcome research dealing with all aspects of non-coding RNAs-their biogenesis, regulation and role in disease progression. The focus of this journal will be to publish translational studies as well as well-designed basic studies with translational and clinical implications. The non-coding RNAs of particular interest will be microRNAs (miRNAs), small interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), U-RNAs/small nuclear RNAs (snRNAs), exosomal/extracellular RNAs (exRNAs), Piwi-interacting RNAs (piRNAs) and long non-coding RNAs. Topics of interest will include, but not limited to: -Regulation of non-coding RNAs -Targets and regulatory functions of non-coding RNAs -Epigenetics and non-coding RNAs -Biological functions of non-coding RNAs -Non-coding RNAs as biomarkers -Non-coding RNA-based therapeutics -Prognostic value of non-coding RNAs -Pharmacological studies involving non-coding RNAs -Population based and epidemiological studies -Gene expression / proteomics / computational / pathway analysis-based studies on non-coding RNAs with functional validation -Novel strategies to manipulate non-coding RNAs expression and function -Clinical studies on evaluation of non-coding RNAs The journal will strive to disseminate cutting edge research, showcasing the ever-evolving importance of non-coding RNAs in modern day research and medicine.