背景:心脏粘液瘤是心脏的原发性肿瘤。它的起源,原发性心脏肿瘤的罕见发生以及它可能与有限的心脏再生潜力有关,还没有完全知道。这项研究调查了关键的心脏基因/转录因子(TFs)和信号通路,以了解这些重要问题。
方法:包括PubMed、MEDLINE,谷歌学者在没有任何日期限制的情况下搜索已发表的文章,涉及心脏粘液瘤,心脏基因/TFs/信号通路及其在心脏发生中的作用,扩散,分化,关键的相互作用和肿瘤发生,专注于心肌细胞。
结果:心脏遗传景观受增殖和分化相关基因/TFs/途径之间非常严格的控制。心脏粘液瘤的起源可能是由于分化调节因子基因表达失调的结果,包括Tbx5,GATA4,HAND1/2,MYOCD,HOPX,BMP。这种失调通过失调Isl1,Baf60复合物,将心肌细胞的表达转换为心脏粘液瘤发育中的祖细胞样状态,Wnt,FGF,缺口,mef2c和其他。Nkx2-5和MSX2主要有助于心脏祖细胞(CPCs)的增殖和分化,根据微环境和细胞回路的方向,可能在心脏肿瘤发生中起作用。心脏粘液瘤中的Nkx2-5可能会限制肿瘤发生的进展,因为它对CPC的增殖有很大的控制。心脏细胞类型特异性遗传编程在控制肿瘤发生和再生潜力中起着主导作用。
结论:心肌细胞具有非常有限的增殖和再生潜能。它们长时间存活并紧密维持分化基因如Tbx5、GATA4的基因表达,其与肿瘤抑制因子(TS)相互作用并发挥TS样效应。这种基因表达所发挥的总作用是原发性心脏肿瘤的罕见发生和良性性质的原因。这阻止了肿瘤发生的进展。但这也限制了心肌细胞的再生和增殖潜力。心脏粘液瘤的发展是由于这些关键基因的失调而导致的,这些关键基因使细胞恢复为祖细胞样状态,CM的标志。Carney复合物中的CM发育也表明TS在心脏细胞中的作用。
BACKGROUND: Cardiac Myxoma is a primary tumor of heart. Its origins, rarity of the occurrence of primary cardiac tumors and how it may be related to limited cardiac regenerative potential, are not yet entirely known. This study investigates the key cardiac genes/ transcription factors (TFs) and signaling pathways to understand these important questions.
METHODS: Databases including PubMed, MEDLINE, and Google Scholar were searched for published articles without any date restrictions, involving cardiac myxoma, cardiac genes/TFs/signaling pathways and their roles in
cardiogenesis, proliferation, differentiation, key interactions and tumorigenesis, with focus on cardiomyocytes.
RESULTS: The cardiac genetic landscape is governed by a very tight control between proliferation and differentiation-related genes/TFs/pathways. Cardiac myxoma originates possibly as a consequence of dysregulations in the gene expression of differentiation regulators including Tbx5, GATA4, HAND1/2, MYOCD, HOPX, BMPs. Such dysregulations switch the expression of cardiomyocytes into progenitor-like state in cardiac myxoma development by dysregulating Isl1, Baf60 complex, Wnt, FGF, Notch, Mef2c and others. The Nkx2-5 and MSX2 contribute predominantly to both proliferation and differentiation of Cardiac Progenitor Cells (CPCs), may possibly serve roles based on the microenvironment and the direction of cell circuitry in cardiac tumorigenesis. The Nkx2-5 in cardiac myxoma may serve to limit progression of tumorigenesis as it has massive control over the proliferation of CPCs. The cardiac cell type-specific genetic programming plays governing role in controlling the tumorigenesis and regenerative potential.
CONCLUSIONS: The cardiomyocytes have very limited proliferative and regenerative potential. They survive for long periods of time and tightly maintain the gene expression of differentiation genes such as Tbx5, GATA4 that interact with tumor suppressors (TS) and exert TS like effect. The total effect such gene expression exerts is responsible for the rare occurrence and benign nature of primary cardiac tumors. This prevents the progression of tumorigenesis. But this also limits the regenerative and proliferative potential of cardiomyocytes. Cardiac Myxoma develops as a consequence of dysregulations in these key genes which revert the cells towards progenitor-like state, hallmark of CM. The CM development in carney complex also signifies the role of TS in cardiac cells.