MiR-153 reduces stem cell-like phenotype and tumor growth of lung adenocarcinoma by targeting Jagged1
Open Access
- 6 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Stem Cell Research & Therapy
- Vol. 11 (1), 1-12
- https://doi.org/10.1186/s13287-020-01679-7
Abstract
Cancer stem cells (CSCs) have been proposed to be responsible for tumor recurrence and chemo-resistance. Previous studies suggested that miR-153 played essential roles in lung cancer. However, the molecular mechanism of miR-153 in regulating the stemness of non-small cell lung cancer (NSCLC) remains poorly understood. In this study, we investigated the role of miR-153 in regulation of the stemness of NSCLC. The stemness property of lung stem cancer cells was detected by sphere formation assay, immunofluorescence, and Western blot. Luciferase reporter assay was performed to investigate the direct binding of miR-153 to the 3′-UTR of JAG1 mRNA. Animal study was conducted to evaluate the effect of miR-153 on tumor growth in vivo. The clinical relevance of miR-153 in NSCLC was evaluated by Rt-PCR and Kaplan-Meier analysis. MiR-153 expression was decreased in lung cancer tissues. Reduced miR-153 expression was associated with lung metastasis and poor overall survival of lung cancer patients. Jagged1, one of the ligands of Notch1, is targeted by miR-153 and inversely correlates with miR-153 in human lung samples. More importantly, we found that miR-153 inhibited stem cell-like phenotype and tumor growth of lung adenocarcinoma through inactivating the Jagged1/Notch1 axis. MiR-153 suppresses the stem cell-like phenotypes and tumor growth of lung adenocarcinoma by targeting Jagged1 and provides a potential therapeutic target in lung cancer therapy.Funding Information
- National Natural Science Foundation of China (81403150)
- Natural Science Foundation of Shandong Province of China (ZR2014HL064)
- Traditional Chinese Medical Sciences and Technology of Shandong Province (2015-325)
- Key R & D project of Shandong Province (2016ZDJSO7A15)
- Innovation Project of Shandong Academy of Medical Sciences (2019)
This publication has 42 references indexed in Scilit:
- Aberrant microRNAs Expression in CD133+/CD326+ Human Lung Adenocarcinoma Initiating Cells from A549Molecules and Cells, 2012
- Prognostic impact of Notch ligands and receptors in nonsmall cell lung cancerCancer, 2010
- EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancerOncogene, 2010
- Highly tumorigenic lung cancer CD133 + cells display stem-like features and are spared by cisplatin treatmentProceedings of the National Academy of Sciences of the United States of America, 2009
- Cell and molecular biology of NotchJournal of Endocrinology, 2007
- MicroRNA Signatures in Human CancersNature Reviews Cancer, 2006
- Cancer Stem Cells—Perspectives on Current Status and Future Directions: AACR Workshop on Cancer Stem CellsCancer Research, 2006
- Notch signalling: a simple pathway becomes complexNature Reviews Molecular Cell Biology, 2006
- The MicroRNA Pathway Plays a Regulatory Role in Stem Cell DivisionCell Cycle, 2005
- MicroRNAs: Genomics, Biogenesis, Mechanism, and FunctionCell, 2004