The LGMN pseudogene promotes tumor progression by acting as a miR-495-3p sponge in glioblastoma
The LGMN pseudogene promotes tumor progression by acting as a miR-495-3p sponge in glioblastoma
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LGMN 假基因在胶质母细胞瘤中充当 miR-495-3p 海绵，促进肿瘤进展
DOI：
10.1016/j.canlet.2020.07.012
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发表时间：
2020-10-10
期刊：
影响因子：
9.7
通讯作者：
Lin, Yingying
中科院分区：
文献类型：
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作者：
Liao, Keman;Qian, Zhongrun;Lin, Yingying
假基因是由蛋白质编码基因产生的长链非编码RNA，被认为在疾病中起着重要作用。尽管研究已经揭示了Legumain（LGMN）在许多类型的肿瘤中的高表达，但LGMN的调节仍然在很大程度上未知。在这里，我们发现一种新的LGMN假基因（LGMNP 1）在胶质母细胞瘤（GBM）组织中上调，并且LGMNP 1在GBM细胞中的高表达增强了增殖和侵袭。生化分析表明，胞质LGMNP 1以涉及RNA诱导沉默复合物的方式功能性靶向miR-495- 3 p。双荧光素酶报告基因分析表明LGMN是miR-495- 3 p的靶点，并且LGMN在GBM中上调并与LGMNP 1正相关。此外，miR-495- 3 p在GBM组织中下调，并与LGMNP 1呈负相关。值得注意的是，LGMNP 1上调的肿瘤促进作用可以通过miR-495- 3 p模拟物减轻。此外，过表达LGMNP 1的GBM细胞在体内表现出更侵袭性的肿瘤进展和升高的LGMN表达。因此，我们的数据表明，LGMNP 1发挥其致癌活性，至少部分，作为一个竞争性的内源性RNA（ceRNA），提高LGMN的表达海绵miR-495- 3 p。CeRNA介导的miRNA螯合可能是GBM的一种新的治疗策略。
Pseudogenes, which are long noncoding RNAs that originate from protein-coding genes, have been suggested to play important roles in disease. Although studies have revealed high expression of legumain (LGMN) in many types of tumors, the regulation of LGMN remains largely unknown. Here, we found that a novel LGMN pseudogene (LGMNP1) was upregulated in glioblastoma (GBM) tissues and high LGMNP1 expression in GBM cells enhanced proliferation and invasion. Biochemical analysis showed that cytoplasmic LGMNP1 functionally tar geted miR-495-3p in a manner involving an RNA-induced silencing complex. Dual-luciferase reporter assays demonstrated that LGMN was a target of miR-495-3p, and LGMN was upregulated and positively correlated with LGMNP1 in GBM. Moreover, miR-495-3p was downregulated and negatively correlated with LGMNP1 in GBM tissues. Notably, the tumor-promoting effects of LGMNP1 upregulation could be alleviated by miR-495-3p mimics. Furthermore, GBM cells overexpressing LGMNP1 exhibited more aggressive tumor progression and elevated LGMN expression in vivo. Thus, our data illustrate that LGMNP1 exerts its oncogenic activity, at least in part, as a competitive endogenous RNA (ceRNA) that elevates LGMN expression by sponging miR-495-3p. CeRNA-mediated miRNA sequestration might be a novel therapeutic strategy in GBM.