Long non-coding RNA FENDRR attenuates the sternness of non-small cell lung cancer cells via decreasing multidrug resistance gene 1 (MDR1) expression through competitively binding with RNA binding protein HuR
Long non-coding RNA FENDRR attenuates the sternness of non-small cell lung cancer cells via decreasing multidrug resistance gene 1 (MDR1) expression through competitively binding with RNA binding protein HuR
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DOI：
10.1016/j.ejphar.2019.04.022
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发表时间：
2019-06-15
影响因子：
5
通讯作者：
Xu, Weiling
中科院分区：
文献类型：
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作者：
Gong, Fangchao;Dong, Dong;Xu, Weiling
长链非编码RNA（lncRNA）FENDRR在非小细胞肺癌（NSCLC）细胞进展中的作用尚未被揭示。由于癌症干细胞（CSC）在肿瘤进展中起着重要作用，因此，我们将重点放在FENDRR在NSCLC细胞干性中的作用。我们发现lncRNA FENDRR在肺癌组织和细胞中的表达显著降低，尤其是在NSCLC细胞中。然后，我们构建了FENDRR稳定过表达的NSCLC细胞，并显示FENDRR过表达减弱了NSCLC细胞的干细胞性，这通过干细胞性标志物表达和细胞球体形成能力的降低来证明。在机制上，我们发现FENDRR可以直接特异性地与多药耐药基因1（MDR 1）的3 '非翻译区（3'UTR）结合，阻碍RNA结合蛋白HuR与MDR 1 3'UTR的结合，从而降低MDR 1的表达。最后，我们证明了FENDRR通过HuR/MDR1轴对NSCLC细胞的干细胞性发挥作用。我们的研究结果表明，FENDRR通过抑制HuR/MDR1轴来减弱NSCLC细胞的干细胞性。
The roles of long non-coding RNA (lncRNA) FENDRR in non-small cell lung cancer (NSCLC) cells progression have never been revealed. As cancer stem cells (CSCs) act important roles in tumor progression, here, we focused on FENDRR roles in NSCLC cell stemness. We found that lncRNA FENDRR expression was significantly decreased in lung cancer tissues and cells, especially in NSCLC cells. Then we constructed NSCLC cells with FENDRR stable overexpression and revealed that FENDRR overexpression attenuated the stemness of NSCLC cells, evident by decreased stemness markers expression and capacity of cell spheroid formation. Mechanistically, we found that FENDRR could directly and specifically bind to the 3' untranslated region (3'UTR) of multidrug resistance gene 1 (MDR1), hinder the binding of RNA binding protein HuR to MDR1 3'UTR and thus decrease MDR1 expression. Finally, we demonstrated that FENDRR exerted its effects on NSCLC cell stemness through the HuR/MDR1 axis. Our results suggest that FENDRR attenuates NSCLC cell stemness through inhibiting the HuR/MDR1 axis.