Lu Jiaojiao, Zheng Xia, Li Xu
Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Department of Gynecology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China.
Discov Oncol. 2025 Jun 14;16(1):1097. doi: 10.1007/s12672-025-02933-1.
Long non-coding RNAs (lncRNAs) have been extensively studied and are recognized for their crucial roles in cancer development. Among them, lncRNA SRRM2-AS1 has emerged as a significant factor, yet its functions in ovarian cancer remain insufficiently understood.
We analyzed SRRM2-AS1 expression and genetic alterations using data from TCGA, GEO, and cBioPortal. Enrichment analyses of differentially expressed genes (DEGs) associated with SRRM2-AS1 were conducted via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Immune cell infiltrations were assessed with the single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm, while subcellular localization was predicted using the lncATLAS database. We conducted qRT-PCR and fluorescence in situ hybridization (FISH) to examine the expression and localization of SRRM2-AS1. Cellular assays were performed to assess the impact of SRRM2-AS1 inhibition in ovarian cancer.
SRRM2-AS1 expression was significantly elevated in ovarian cancer tissues compared to normal tissues, as evidenced by data from TCGA, GTEx, and supported by the GSE18520 and GSE40595 datasets, along with our own samples (14 ovarian cancer tissues and 9 normal tissues). Receiver operating characteristic (ROC) analysis indicated its potential as a diagnostic biomarker with an Area Under the Curve (AUC) of 0.758. We identified 957 DEGs associated with SRRM2-AS1, with GO and KEGG enrichment analyses highlighting their involvement in microtubule-based movement, cilium movement and immune cell interactions. Immune infiltration analyses indicated significant correlations between SRRM2-AS1 expression and various immune cell types, suggesting its role in modulating the tumor microenvironment. Subcellular localization studies using the lncATLAS database, qRT-PCR, and FISH confirmed the nuclear predominance of SRRM2-AS1 in ovarian cancer cells. Functionally, SRRM2-AS1 knockdown inhibited ovarian cancer cell proliferation, migration, and invasion.
These findings underscore the potential of SRRM2-AS1 as both a biomarker and a therapeutic target in ovarian cancer, highlighting the need for further investigation into its mechanistic roles and clinical applications.
长链非编码RNA（lncRNAs）已得到广泛研究，并因其在癌症发展中的关键作用而受到认可。其中，lncRNA SRRM2-AS1已成为一个重要因素，但其在卵巢癌中的功能仍未得到充分了解。
我们使用来自TCGA、GEO和cBioPortal的数据，分析了SRRM2-AS1的表达和基因改变。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）对与SRRM2-AS1相关的差异表达基因（DEGs）进行了富集分析。使用单样本基因集富集分析（ssGSEA）算法评估免疫细胞浸润情况，同时使用lncATLAS数据库预测亚细胞定位。我们进行了qRT-PCR和荧光原位杂交（FISH），以检测SRRM2-AS1的表达和定位。进行细胞实验以评估SRRM2-AS1抑制对卵巢癌的影响。
与正常组织相比，TCGA、GTEx的数据以及GSE18520和GSE40595数据集以及我们自己的样本（14个卵巢癌组织和9个正常组织）均证明，卵巢癌组织中SRRM2-AS1的表达显著升高。受试者工作特征（ROC）分析表明其作为诊断生物标志物的潜力，曲线下面积（AUC）为0.758。我们鉴定出957个与SRRM2-AS1相关的DEGs，GO和KEGG富集分析突出了它们参与基于微管的运动、纤毛运动和免疫细胞相互作用。免疫浸润分析表明SRRM2-AS1表达与多种免疫细胞类型之间存在显著相关性，表明其在调节肿瘤微环境中的作用。使用lncATLAS数据库、qRT-PCR和FISH进行的亚细胞定位研究证实了SRRM2-AS1在卵巢癌细胞中主要位于细胞核。在功能上，SRRM2-AS1敲低抑制了卵巢癌细胞的增殖、迁移和侵袭。
这些发现强调了SRRM2-AS1作为卵巢癌生物标志物和治疗靶点的潜力，突出了进一步研究其机制作用和临床应用的必要性。
