The impact of SRRM2-AS1 in ovarian cancer: a comprehensive analysis based on pan-cancer and in vitro validation

SRRM2-AS1在卵巢癌中的作用:基于泛癌和体外验证的综合分析

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作者:Jiaojiao Lu,Xia Zheng,Xu Li

Abstract

Background: 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. Materials and methods: 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. Results: 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. Conclusion: 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.

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