miR-30 Family Reduction Maintains Self-Renewal and Promotes Tumorigenesis in NSCLC-Initiating Cells by Targeting Oncogene TM4SF1

Increasing evidence indicates that tumor-initiating cells (TICs) are responsible for the occurrence, development, recurrence, and development of the drug resistance of cancer. MicroRNA (miRNA) plays a significant functional role by directly regulating targets of TIC-triggered non-small-cell lung can...

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Veröffentlicht in:Molecular therapy 2018-12, Vol.26 (12), p.2751-2765
Hauptverfasser: Ma, Yu-Shui, Yu, Fei, Zhong, Xiao-Ming, Lu, Gai-Xia, Cong, Xian-Ling, Xue, Shao-Bo, Xie, Wen-Ting, Hou, Li-Kun, Pang, Li-Juan, Wu, Wei, Zhang, Wei, Cong, Le-Le, Liu, Tie, Long, Hui-Deng, Sun, Ran, Sun, Hong-Yan, Lv, Zhong-Wei, Wu, Chun-Yan, Fu, Da
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Sprache:eng
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Zusammenfassung:Increasing evidence indicates that tumor-initiating cells (TICs) are responsible for the occurrence, development, recurrence, and development of the drug resistance of cancer. MicroRNA (miRNA) plays a significant functional role by directly regulating targets of TIC-triggered non-small-cell lung cancer (NSCLC), but little is known about the function of the miR-30 family in TICs. In this study, we found the miR-30 family to be downregulated during the spheroid formation of NSCLC cells, and patients with lower miR-30a/c expression had shorter overall survival (OS) and progression-free survival (PFS). Moreover, transmembrane 4 super family member 1 (TM4SF1) was confirmed to be a direct target of miR-30a/c. Concomitant low expression of miR-30a/c and high expression of TM4SF1 correlated with a shorter median OS and PFS in NSCLC patients. miR-30a/c significantly inhibited stem-like characteristics in vitro and in vivo via suppression of its target gene TM4SF1, and then it inhibited the activity of the mTOR/AKT-signaling pathway. Thus, our data provide the first evidence that TM4SF1 is a direct target of miR-30a/c and miR-30a/c inhibits the stemness and proliferation of NSCLC cells by targeting TM4SF1, suggesting that miR-30a/c and TM4SF1 may be useful as tumor biomarkers for the diagnosis and treatment of NSCLC patients. miRNAs play a significant functional role in TIC-triggered NSCLC. Herein, Ma et al. demonstrate that TM4SF1 is a direct target of miR-30a/c and miR-30a/c inhibits the stemness and proliferation of NSCLC cells by targeting TM4SF1, suggesting that miR-30a/c and TM4SF1 may be useful as tumor biomarkers for NSCLC.
ISSN:1525-0016
1525-0024
DOI:10.1016/j.ymthe.2018.09.006