The ratio of FoxA1 to FoxA2 in lung adenocarcinoma is regulated by LncRNA HOTAIR and chromatin remodeling factor LSH.
The ratio of FoxA1 to FoxA2 in lung adenocarcinoma is regulated by LncRNA HOTAIR and chromatin remodeling factor LSH.
复制标题
肺腺癌中FoxA1与FoxA2的比例受LncRNA HOTAIR和染色质重塑因子LSH的调节
DOI：
10.1038/srep17826
复制
发表时间：
2015-12-11
影响因子：
4.6
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Wang R;Shi Y;Chen L;Jiang Y;Mao C;Yan B;Liu S;Shan B;Tao Y;Wang X
lncRNA HOTAIR是癌症进展的关键调节因子。染色质重塑因子LSH对植物和哺乳动物的正常发育至关重要。然而，导致癌症发生这种情况的潜在机制尚不完全清楚。FOXA 1和FOXA 2的功能多样性有助于靶基因在进化和癌变过程中的作用。关于FOXA 1与FOXA 2在癌症中的比例知之甚少。我们发现HOTAIR和LSH过表达与肺腺癌患者的生存率显著相关。此外，FOXA 1和FOXA 2的比例与肺ADC患者的生存率低有关。HOTAIR调节FOXA 1与FOXA 2的比例以及迁移和侵袭。HOTAIR与FOXA 1/FOXA 2比值呈负相关。HOTAIR敲低抑制迁移和侵袭。HOTAIR与LSH相关，这种关联与FOXA 1启动子中LSH的结合有关，而不是FOXA 2。HOTAIR的靶向抑制可抑制迁移和侵袭特性。这些数据表明HOTAIR是FOXA 1和FOXA 2比例的重要介质，LSH参与其中，并表明HOTAIR抑制可能代表抑制肺ADC进展的有希望的治疗选择。
The lncRNA HOTAIR is a critical regulator of cancer progression. Chromatin remodeling factor LSH is critical for normal development of plants and mammals. However, the underlying mechanisms causing this in cancer are not entirely clear. The functional diversification of the FOXA1 and FOXA2 contributes to the target genes during evolution and carcinogenesis. Little is known about the ratio of FOXA1 to FOXA2 in cancer. We here found that both HOTAIR and LSH overexpression was significantly correlated with poor survival in patients with lung adenocarcinoma cancer (ADC). Also, the ratio of FOXA1 and FOXA2 is linked with poor survival in patients with lung ADC. HOTAIR regulates the ratio of FOXA1 to FOXA2 and migration and invasion. HOTAIR and the ratio of FOXA1 to FOXA2 are negatively correlated. HOTAIR knockdown inhibits migration and invasion. HOTAIR is associated with LSH and this association linked with the binding of LSH in the promoter of FOXA1, not FOXA2. Targeted inhibition of HOTAIR suppresses the migratory and invasive properties. These data suggest that HOTAIR is an important mediator of the ratio of FOXA1 and FOXA2 and LSH involves in and suggest that HOTAIR inhibition may represent a promising therapeutic option for suppressing lung ADC progression.