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长链非编码 RNA ENST00000503625 是前列腺癌的一个潜在预后标志物和转移抑制基因。

Long non-coding RNA ENST00000503625 is a potential prognostic biomarker and metastasis suppressor gene in prostate cancer.

机构信息

Department of Urology, Institute of Surgery Research, Daping Hospital/Army Medical Center, Army Medical University, Chongqing, 400042, China.

Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.

出版信息

J Cancer Res Clin Oncol. 2023 Aug;149(10):7305-7317. doi: 10.1007/s00432-023-04676-4. Epub 2023 Mar 15.

Abstract

BACKGROUND

Dysregulation of Long Non-coding RNAs (lncRNAs) emerges to be a hallmark of cancers. Metastatic prostate cancer and localized disease that recurs after treatment are clinical challenges, it remains unclear how lncRNA plays a role in those processes.

METHODS

From previous RNA-Seq data on 65 prostate cancer and adjacent normal tissues. We identified a novel lncRNA ENST00000503625 down-regulated in prostate cancer and correlated with tumor progression characteristics. Public datasets were examined for associations between ENST00000503625 expression and clinical parameters and prognoses. Subsequently, we constructed and externally validated a nomogram for predicting biochemical recurrence (BCR). Finally, in vitro experiments were carried out to determine how ENST00000503625 functions biologically in prostate cancer.

RESULTS

Low ENST00000503625 in tumor was associated with poor clinical features and prognoses. TCGA pan-cancer analysis found that ENST00000503625 was deregulated in a variety of tumors and correlated with overall survival, disease-specific survival, and progression-free survival. The nomogram for predicting BCR was constructed using TCGA data, which exhibited excellent accuracy in external validation with Chinese Prostate Cancer Genome and Epigenome Atlas data. Gene Ontology and KEGG pathway analysis found that genes related to ENST00000503625 were enriched in multiple tumor progression related pathways. When ENST00000503625 was knocked down in vitro, the epithelial-mesenchymal transition was induced, by which cancer cells migrated and invaded more readily.

CONCLUSION

Our data suggested that ENST00000503625 may serve as a potential prognostic marker or a therapeutic target for prostate cancer metastases.

摘要

背景

长非编码 RNA(lncRNA)的失调已成为癌症的标志。转移性前列腺癌和治疗后复发的局限性疾病是临床挑战,lncRNA 在这些过程中如何发挥作用尚不清楚。

方法

从 65 例前列腺癌和相邻正常组织的 RNA-Seq 数据中。我们鉴定了一种在前列腺癌中下调且与肿瘤进展特征相关的新型 lncRNA ENST00000503625。检查了公共数据集,以确定 ENST00000503625 表达与临床参数和预后之间的关联。随后,我们构建并外部验证了用于预测生化复发(BCR)的列线图。最后,进行了体外实验以确定 ENST00000503625 在前列腺癌中的生物学功能。

结果

肿瘤中低表达的 ENST00000503625 与不良的临床特征和预后相关。TCGA 泛癌分析发现,ENST00000503625 在多种肿瘤中失调,与总生存期、疾病特异性生存期和无进展生存期相关。使用 TCGA 数据构建了用于预测 BCR 的列线图,该图在使用中国前列腺癌基因组和表观基因组图谱数据进行外部验证时表现出优异的准确性。基因本体论和 KEGG 通路分析发现,与 ENST00000503625 相关的基因富集在多个肿瘤进展相关通路中。当在体外敲低 ENST00000503625 时,上皮-间充质转化被诱导,从而使癌细胞更容易迁移和侵袭。

结论

我们的数据表明,ENST00000503625 可能作为前列腺癌转移的潜在预后标志物或治疗靶点。

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