lncRNA FENDRR通过HuR/MDR1轴减弱非小细胞肺癌细胞干性的机制
Long non-coding RNA FENDRR attenuates the stemness of non-small cell lung cancer cells via decreasing multidrug resistance gene 1 (MDR1) expression through competitively binding with RNA binding protein HuR
Fangchao Gong, Dong Dong, Ting Zhang, Weiling Xu
Journal:EUROPEAN JOURNAL OF PHARMACOLOGY
IF:3.17
DOI:10.1016/j.ejphar.2019.04.022
PMID:30981768
Published:2019-04-11
research field:组织培养生物医学工程再生医学增材制造材料科学
Abstract
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.
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