Tongji University School of Medicine, Shanghai, 200092, China.
Department of Gastroenterology, Tongji Hospital of Tongji University, Shanghai, 200065, China.
Bioengineered. 2021 Dec;12(2):10564-10586. doi: 10.1080/21655979.2021.2000226.
Aberrant expression of long non-coding RNAs (lncRNAs) is involved in the progression of myeloid neoplasms, but the role of lncRNAs in the JAK2V617F-positive subtype of classical myeloproliferative neoplasms (cMPNs) remains unclear. This study was conducted to clarify the expression and regulation patterns of lncRNAs in JAK2V617F-positive cMPNs, and to explore new potential carcinogenic factors of cMPNs. Bioinformatics analysis of microarray detection and wet testing verification were performed to study the expression and regulation signature of differentially expressed lncRNAs (DELs) and related genes (DEGs) in cMPNs. The expression of lncRNAs and mRNAs were observed to significantly dysregulated in JAK2V617F-positive cMPN patients compared with the normal controls. Co-expression analysis indicated that there were significant differences of the co-expression pattern of lncRNAs and mRNAs in JAK2V617F-positive cMPN patients compared to normal controls. GO and KEGG pathway analysis of DEGs and DELs showed the involvement of several pathways previously reported to regulate the pathogenesis of leukemia and cMPNs. Cis- and trans-regulation analysis of lncRNAs showed that ZNF141, DHX29, NOC2L, MAS1L, AFAP1L1, and CPN2 were significantly cis-regulated by lncRNA ENST00000356347, ENST00000456816, hsa-mir-449c, NR_026874, TCONS_00012136, uc003lqp.2, and ENST00000456816, respectively, and DELs were mostly correlated with transcription factors including CTBP2, SUZ12, REST, STAT2, and GATA4 to jointly regulate multiple target genes. In summary, expression profiles of lncRNAs and mRNAs were significantly altered in JAK2V617F-positive cMPNs, the relative signaling pathway, co-expression, cis- and trans-regulation were regulated by dysregulation of lncRNAs and several important genes, such as ITGB3, which may act as a promising carcinogenic factor, warrant further investigation.
长链非编码 RNA（lncRNA）的异常表达参与了骨髓增生性肿瘤的进展，但 lncRNA 在 JAK2V617F 阳性经典骨髓增生性肿瘤（cMPN）亚型中的作用尚不清楚。本研究旨在阐明 JAK2V617F 阳性 cMPN 中 lncRNA 的表达和调控模式，并探索 cMPN 的新潜在致癌因素。通过微阵列检测的生物信息学分析和湿试验验证，研究了 cMPN 中差异表达的 lncRNA（DEL）和相关基因（DEG）的表达和调控特征。与正常对照相比，JAK2V617F 阳性 cMPN 患者的 lncRNA 和 mRNA 表达明显失调。共表达分析表明，JAK2V617F 阳性 cMPN 患者与正常对照之间 lncRNA 和 mRNA 的共表达模式存在显著差异。DEG 和 DEL 的 GO 和 KEGG 通路分析表明，几个通路参与了调节白血病和 cMPN 发病机制的先前报道。lncRNA 的顺式和反式调控分析表明，ZNF141、DHX29、NOC2L、MAS1L、AFAP1L1 和 CPN2 分别被 lncRNA ENST00000356347、ENST00000456816、hsa-mir-449c、NR_026874、TCONS_00012136 和 uc003lqp.2 显著顺式调控，而 DELs 与包括 CTBP2、SUZ12、REST、STAT2 和 GATA4 在内的转录因子大多相关，共同调控多个靶基因。总之，JAK2V617F 阳性 cMPN 中 lncRNA 和 mRNA 的表达谱明显改变，相对信号通路、共表达、顺式和反式调控受 lncRNA 和 ITGB3 等几个重要基因的失调调节，可能作为有前途的致癌因素，值得进一步研究。
