lncRNA–mRNA Expression Patterns in Invasive Pituitary Adenomas: A Microarray Analysis

Abstract

Background. Long noncoding RNAs (lncRNAs) play important roles in the tumorigenesis and progression of various cancer types; however, their roles in the development of invasive pituitary adenomas (PAs) remain to be investigated. Methods. lncRNA microarray analysis was performed for three invasive and three noninvasive PAs. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed, and coexpression networks between lncRNA and mRNA were constructed. Furthermore, three differentially expressed lncRNAs were selected for validation in PA samples by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic values of these three lncRNAs were further evaluated by a receiver operating characteristic (ROC) curve analysis. Results. A total of 8872 lncRNAs were identified in invasive and paired noninvasive PAs via lncRNA microarray analysis. Among these, the differentially expressed lncRNAs included 81 that were upregulated and 165 that were downregulated. GO enrichment and KEGG pathway analysis showed that these differentially expressed lncRNAs were associated with the posttranslational modifications of proteins. Furthermore, we performed target gene prediction and coexpression analysis. The interrelationships between the significantly differentially expressed lncRNAs and mRNAs were identified. Additionally, three differentially expressed lncRNAs were selected for validation in 41 PA samples by qRT-PCR. The expression levels of FAM182B, LOC105371531, and LOC105375785 were significantly lower in the invasive PAs than in the noninvasive PAs ( P < 0.05 ). These results were consistent with the microarray data. ROC curve analysis suggested that the expression levels of FAM182B and LOC105375785 could be used to distinguish invasive PAs from noninvasive PAs. Conclusion. Our findings demonstrated the expression patterns of lncRNAs in invasive PAs. FAM182B and LOC105375785 may be involved in the invasiveness of PAs and serve as new candidate biomarkers for the diagnosis of invasive PAs.

Recent advances in understanding and managing pituitary adenomas

“…miRNAs are small protein non-coding RNAs that regulate gene expression post-transcriptionally, and their abnormal expression has been associated with progress of PAs 9 . Divergent lncRNAs have been found in invasive PAs 10 , and different miRNAs are overexpressed in the three PA clusters. The ACTH adenoma group overexpresses miR4501; CNFPA upregulates miR582, miR4774, and LINC01351 ; while the GH, TSH, and PRL adenoma cluster overexpresses miR377 and miR136 5 .…”

Regulation of long noncoding RNAs in the pathogenesis and clinical implications of pituitary adenomas

“…53 Among them, two lncRNAs, FAM182B and LOC105375785, were found to be involved in the invasiveness of PA and might serve as promising candidate biomarkers for the diagnosis of IPAs. 53 Another transcriptome sequencing study found 70 differentially expressed lncRNAs between invasive and noninvasive GH-PAs, wherein epithelial cell differentiation and development pathways were restrained in invasive GH-PAs by functional annotations and enrichment analysis. 54 Decreased expression of lncRNA SPINT1-AS1 was suggested to serve as an indicator of invasive GH-PAs independent of the unfavorable prognosis.…”

Emerging Roles of miRNA, lncRNA, circRNA, and Their Cross-Talk in Pituitary Adenoma

“…The most significantly DE lncRNA, n334366, is a unique satellite in the co-expression network, where it is related to the neuroactive ligand–receptor interaction pathways [ 84 ]. Subsequently, a total of 246 DE lncRNAs were identified between IPA and NIPA using a lncRNA microarray analysis [ 85 ]. The LOC105371531, LOC105375785, and FAM182B expression levels were significantly decreased in IPA compared to NIPA according to qRT-PCR [ 85 ].…”

“…Subsequently, a total of 246 DE lncRNAs were identified between IPA and NIPA using a lncRNA microarray analysis [ 85 ]. The LOC105371531, LOC105375785, and FAM182B expression levels were significantly decreased in IPA compared to NIPA according to qRT-PCR [ 85 ]. ROC curve analysis showed that the expression of LOC105375785 and FAM182B could distinguish IPA from NIPA, suggesting that LOC105375785 and FAM182B might be implicated in the invasiveness of IPAs and might be novel biomarkers for the diagnosis of IPAs.…”

“…The abundance of DE ncRNAs in PA has been widely reported. Investigating the roles of ncRNAs is helpful for understanding the occurrence and development of PA, and some ncRNAs can be used as biomarkers for the detection of PA [ 1 , 18 , 43 , 127 ], while other ncRNAs can contribute to the diagnosis of PA [ 52 , 85 , 90 , 112 ], distinguish the disease subtypes [ 24 , 25 , 34 , 93 ], and predict tumor invasion and progression [ 20 , 26 , 35 , 85 , 95 , 110 , 111 , 123 ]; the remaining ncRNAs may be implicated in the pathogenesis of PA [ 116 , 117 , 120 , 122 ]. In addition, the regulatory networks of lncRNA/circRNA and miRNA provide promising biomarkers for the noninvasive diagnosis and molecular therapy of PA, and exosome-derived ncRNAs bring a tremendous infusion of hope to the improvement of the disease diagnosis and future potential therapeutic targets for treatments.…”