长链非编码RNA(lncRNAs)在各种生物过程中发挥重要作用,通过多种机制调节基因表达。然而,lncRNAs如何调节肝脏再增殖是未知的。在这里,我们旨在鉴定调节肝脏再增殖的lncRNAs,并阐明相关的信号通路.
这里,我们对野生型和基因敲除小鼠进行了70%的部分肝切除术.然后我们进行转录组学分析以鉴定在肝再生期间高度表达的称为lncHand2的发散lncRNA。
LncHand2在小鼠和人肝脏的中央周围肝细胞核中组成型表达。LncHand2基因敲除消除肝脏再生和再增殖能力。机械上,lncHand2招募Ino80重塑复合物以启动Nkx1-2的反式表达,这触发c-Met(Met)在肝细胞中的表达。最后,敲除Nkx1-2和c-Met会导致更严重的肝损伤和较差的再增殖能力。因此,lncHand2通过启动Nkx1-2诱导的c-Met信号促进肝脏再增殖。
我们的研究结果表明,lncHand2作为调节肝脏再增殖的关键介质。它通过诱导Nkx1-2表达来做到这一点,这反过来又触发c-Met信令。
长链非编码RNA在各种生物过程中发挥重要作用。虽然长链非编码RNA不直接编码蛋白质,它们可以通过多种机制调节基因表达。我们鉴定出长的非编码RNA,被称为lncHand2,因为它与基因Hand2接近,是通过c-Met信号传导肝脏再生的重要决定因素。
Long noncoding RNAs (lncRNAs) play important roles in various biological processes, regulating gene expression by diverse mechanisms. However, how lncRNAs regulate liver repopulation is unknown. Herein, we aimed to identify lncRNAs that regulate liver repopulation and elucidate the signaling pathways involved.
Herein, we performed 70% partial hepatectomy in wild-type and gene knockout mice. We then performed transcriptomic analyses to identify a divergent lncRNA termed lncHand2 that is highly expressed during liver regeneration.
LncHand2 is constitutively expressed in the nuclei of pericentral hepatocytes in mouse and human livers. LncHand2 knockout abrogates liver regeneration and repopulation capacity. Mechanistically, lncHand2 recruits the Ino80 remodeling complex to initiate expression of Nkx1-2 in trans, which triggers c-Met (Met) expression in hepatocytes. Finally, knockout of both Nkx1-2 and c-Met causes more severe liver injury and poorer repopulation ability. Thus, lncHand2 promotes liver repopulation via initiating Nkx1-2-induced c-Met signaling.
Our findings reveal that lncHand2 acts as a critical mediator regulating liver repopulation. It does this by inducing Nkx1-2 expression, which in turn triggers c-Met signaling.
Long noncoding RNAs play important roles in various biological processes. While long noncoding RNAs do not directly code proteins, they can regulate gene expression by diverse mechanisms. We identified the long noncoding RNA, termed lncHand2 because of its proximity to the gene Hand2, to be an important determinant of liver regeneration through c-Met signaling.