Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center and The Lundquist Institute, Torrance, CA, 90502, USA.
Reprod Sci. 2022 Oct;29(10):2960-2976. doi: 10.1007/s43032-022-00981-4. Epub 2022 May 31.
Super-enhancer-associated long non-coding RNAs (SE-lncRNAs) are a specific set of lncRNAs transcribed from super-enhancer (SE) genomic regions. Recent studies have revealed that SE-lncRNAs play essential roles in tumorigenesis through the regulation of oncogenes. The objective of this study was to elucidate the expression profile of SE-lncRNAs with concurrent assessment of associated mRNAs in leiomyomas and paired myometrium. Arraystar SE-lncRNAs arrays were used to systematically profile the differentially expressed SE-lncRNAs along with the corresponding SE-regulated protein coding genes in eight leiomyomas and paired myometrium. The analysis indicated 7680 SE-lncRNAs were expressed, of which 721 SE-lncRNAs were overexpressed, while 247 SE-lncRNAs were underexpressed by 1.5-fold or greater in leiomyoma. Thirteen novel SE-lncRNAs and their corresponding protein coding genes were selected, and their expression was confirmed in eighty-one paired leiomyoma tissues by quantitative real-time PCR. The thirteen pairs of SE-lncRNAs and their corresponding protein coding genes included RP11-353N14.2/CBX4, SOCS2-AS1/SOCS2, RP1-170O19.14/HOXA11, CASC15/PRL, EGFLAM-AS1/EGFLAM, RP11-225H22/NEURL1, RP5-1086K13.1/CD58, AC092839.3/SPTBN1, RP11-69I8.3/CTGF, TM4SF1-AS1/TM4SF1, RP11-373D23/FOSL2, RP11-399K21.11/COMTD1, and CTB-113P19.1/SPARC. Among these SE-lncRNAs, the expression of SOCS2-AS1/SOCS2, RP11-353N14.2/CBX4, RP1-170O19.14/HOXA11, and RP11-225H22/NEURL1 was significantly higher in African Americans as compared with Caucasians. The expression of RP11-353N14.2/CBX4, SOCS2-AS1/SOCS2, CASC15/PRL, and CTB-113P19.1/SPARC was significantly higher in tumors with MED12-mutation-positive as compared with MED12-mutation-negative tumors. Collectively, our results indicate that the differential expression of SE in leiomyomas is another mechanism contributing to dysregulation of protein coding genes in leiomyomas and that race and MED12 mutation can influence the expression of a select group of SE.
超级增强子相关的长非编码 RNA（SE-lncRNAs）是一类从超级增强子（SE）基因组区域转录而来的特定长非编码 RNA。最近的研究表明，SE-lncRNAs 通过调节癌基因在肿瘤发生中发挥重要作用。本研究旨在阐明伴发的 mRNA 在平滑肌瘤和配对的子宫肌层中的表达谱。使用 Arraystar SE-lncRNAs 芯片系统地分析了 8 个平滑肌瘤和配对的子宫肌层中差异表达的 SE-lncRNAs 及其相应的 SE 调节蛋白编码基因。分析表明，有 7680 个 SE-lncRNAs 表达，其中 721 个 SE-lncRNAs 在平滑肌瘤中过表达，而 247 个 SE-lncRNAs 表达下调 1.5 倍或以上。选择了 13 个新的 SE-lncRNAs 及其相应的蛋白编码基因，并通过定量实时 PCR 在 81 对配对的平滑肌瘤组织中证实了其表达。这 13 对 SE-lncRNAs 及其相应的蛋白编码基因包括 RP11-353N14.2/CBX4、SOCS2-AS1/SOCS2、RP1-170O19.14/HOXA11、CASC15/PRL、EGFLAM-AS1/EGFLAM、RP11-225H22/NEURL1、RP5-1086K13.1/CD58、AC092839.3/SPTBN1、RP11-69I8.3/CTGF、TM4SF1-AS1/TM4SF1、RP11-373D23/FOSL2、RP11-399K21.11/COMTD1 和 CTB-113P19.1/SPARC。在这些 SE-lncRNAs 中，SOCS2-AS1/SOCS2、RP11-353N14.2/CBX4、RP1-170O19.14/HOXA11 和 RP11-225H22/NEURL1 的表达在非裔美国人中明显高于白种人。RP11-353N14.2/CBX4、SOCS2-AS1/SOCS2、CASC15/PRL 和 CTB-113P19.1/SPARC 的表达在 MED12 突变阳性肿瘤中明显高于 MED12 突变阴性肿瘤。总的来说，我们的结果表明，平滑肌瘤中 SE 的差异表达是导致平滑肌瘤中蛋白编码基因失调的另一种机制，种族和 MED12 突变可以影响一组选定的 SE 的表达。
