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Identification of ADAMTS9-AS2 and MBNL1-AS1 as subtype-specific dysregulated lncRNAs in basal and luminal muscle-invasive bladder cancer via RNA sequencing

ABSTRACT: Muscle-invasive bladder cancer (MIBC) is an aggressive disease with high morbidity and mortality that can be divided into basal and luminal subtypes based on genomic characteristics. Due to the complex heterogeneity of MIBC, specific markers are needed to distinguish MIBC subtypes to guide future clinical treatment. In this study, we explore abnormal lncrnas that are specific to the basic and intracavitary subtypes of MIBC, which will provide potential biomarkers for precision therapy of MIBC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE229410 | GEO | 2023/04/14

REPOSITORIES: GEO

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Project description:BackgroundLuminal breast cancer (BC) is the most frequent subtype accounting for more than 70% of BC. LncRNAs, a class of non-coding RNAs with more than 200 nucleotides, are involved in a variety of cellular processes and biological functions. Abberant expression is related to the development of various cancers, such as breast cancer. LINC01133, ZEB1-AS1, and ABHD11-AS1 were reported to be dysregulated in different cancers. However, their expression level in luminal BC remains poorly known. The aim of the present study was to evaluate the potential roles of these lncRNAs in BC, especially in luminal subtypes.MethodsA comprehensive analysis was performed using the Lnc2Cancer database to identify novel cancer-associated lncRNA candidates. After conducting a literature review, three novel lncRNAs named LINC01133, ZEB1-AS1, and ABHD11-AS1 were chosen as target genes of the present study. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate the expression level of the mentioned lncRNAs in both luminal BC tissues and cell lines. Then, the correlation of the three mentioned lncRNAs expression with clinicopathological characteristics of the patients was studied. Moreover, several datasets were used to discover the potential roles and functions of LINC01133, ZEB1-AS1 and ABHD11-AS1 in luminal subtype of BC.ResultsAccording to the qRT-PCR assay, the expression levels of LINC01133 and ZEB1-AS1 were decreased in luminal BC tissues and cell lines. On the other hand, ABHD11-AS1 was upregulated in the above-mentioned samples. The expression levels of LINC01133, ZEB1-AS1, and ABHD11-AS1 were not associated with any of the clinical features. Also, the results obtained from the bioinformatics analyses were consistent with qRT-PCR data. Functional annotation of the co-expressed genes with the target lncRNAs, protein-protein interactions and significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways across luminal BC were also obtained using bioinformatics analysis.ConclusionsTaken together, our findings disclosed the dysregulation of LINC01133, ZEB1-AS1, and ABHD11-AS1 in luminal BC. It was revealed that LINC01133 and ZEB1-AS1 expression was significantly downregulated in luminal BC tissues and cell lines, while ABHD11-AS1 was upregulated considerably in the mentioned tissues and cell lines. Also, bioinformatics and systems biology analyses have helped to identify the possible role of these lncRNAs in luminal BC. However, further analysis is needed to confirm the current findings.

Dataset Information

Identification of ADAMTS9-AS2 and MBNL1-AS1 as subtype-specific dysregulated lncRNAs in basal and luminal muscle-invasive bladder cancer via RNA sequencing

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