Long noncoding RNA LHFPL3-AS2 suppresses metastasis of non-small cell lung cancer by interacting with SFPQ to regulate TXNIP expression
Long noncoding RNA LHFPL3-AS2 suppresses metastasis of non-small cell lung cancer by interacting with SFPQ to regulate TXNIP expression
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DOI：
10.1016/j.canlet.2022.01.031
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发表时间：
2022-02-01
期刊：
影响因子：
9.7
通讯作者：
Qin, Wenxin
中科院分区：
文献类型：
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作者：
Cheng, Zhuoan;Lu, Chunlai;Qin, Wenxin
肺癌是世界上最常见的癌症，也是癌症死亡的主要原因。除了编码基因外，长链非编码RNA （lncRNA）在非小细胞肺癌（NSCLC）中的作用尚不清楚。在这里，我们利用Affymetrix基因芯片人类转录组阵列2.0在37对非小细胞肺癌肿瘤组织和邻近非肿瘤组织样本中研究了lncRNA的表达谱。我们发现LHFPL3-AS2是一种新的lncRNA，在NSCLC组织中显著减少。LHFPL3-AS2在另外93例NSCLC配对样本中得到进一步验证。低水平的LHFPL3-AS2表达与NSCLC患者较差的总生存率、TNM分期和转移高度相关。LHFPL3-AS2表达增强对体内外NSCLC侵袭转移有抑制作用。此外，LHFPL3-AS2的下调降低了其与SFPQ的特异性相互作用，导致更多的SFPQ结合到TXNIP的启动子上，从而抑制TXNIP的转录，最终促进NSCLC细胞的迁移和侵袭。此外，LHFPL3AS2在缺氧条件下受到EGR1的调控。
Lung cancer is the most common cancer and the leading cause of cancer deaths worldwide. In addition to coding genes, the contribution of long noncoding RNA (lncRNA) to non-small cell lung cancer (NSCLC) remains unclear. Here, we explored lncRNA expression profiles by Affymetrix Gene Chip Human Transcriptome Array 2.0 in 37 paired samples of tumorous NSCLC tissues and adjacent nontumorous tissues. We showed that LHFPL3-AS2 is a novel lncRNA, significantly decreased in NSCLC tissues. LHFPL3-AS2 was further validated in an additional 93 paired samples of NSCLC. Low levels of LHFPL3-AS2 expression were highly correlated with poor overall survival, TNM stage, and metastasis of NSCLC patients. Enhanced expression of LHFPL3-AS2 inhibited NSCLC invasion and metastasis in vitro and in vivo. Moreover, downregulation of LHFPL3-AS2 reduced its specific interaction with SFPQ, resulting in more SFPQ binding to the promoter of TXNIP and causing the transcriptional repression of TXNIP, thus finally promoting the migration and invasion of NSCLC cells. Furthermore, LHFPL3AS2 was shown to be regulated by EGR1 under hypoxia.