Research Paper Volume 13, Issue 6 pp 8055—8067
Silencing SIX1 by miR-7160 inhibits non-small cell lung cancer cell growth
- 1 Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- 2 Obstetrics and Gynecology Department, The Second Affiliated Hospital of Soochow University, Suzhou, China
- 3 Department of Respiratory Medicine, Affiliated Zhongda Hospital of Southeast University, Nanjing, China
- 4 Department of Endocrinology, Henan Provincial People’s Hospital; People’s Hospital of Zhengzhou University, Zhengzhou, China
- 5 Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Received: June 24, 2020 Accepted: August 15, 2020 Published: March 3, 2021https://doi.org/10.18632/aging.202398
How to Cite
Copyright: © 2021 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The homeoprotein SIX1 is upregulated in non-small cell lung cancer (NSCLC) and associated with NSCLC tumorigenesis and progression. We identified microRNA-7160 (miR-7160) as a SIX1-targeting miRNA. RNA immunoprecipitation results confirmed a direct binding between miR-7160 and SIX1 mRNA in NSCLC cells. In the primary and established NSCLC cells, forced overexpression of miR-7160 downregulated SIX1 and inhibited cancer cell growth, proliferation, migration and invasion. Furthermore, miR-7160 overexpression induced apoptosis activation in NSCLC cells. Conversely, miR-7160 inhibition elevated SIX1 expression and enhanced NSCLC cell progression in vitro. Restoring SIX1 expression, by an untranslated region-depleted SIX1 expression construct, reversed miR-7160-induced anti-NSCLC cell activity. CRISPR/Cas9-inudced knockout of SIX1 mimicked miR-7160-induced actions and produced anti-NSCLC cell activity. In vivo, intratumoral injection of miR-7160-expressing lentivirus downregulated SIX1 mRNA and inhibited NSCLC xenograft growth in severe combined immunodeficient mice. Significantly, miR-7160 expression is downregulated in human NSCLC tissues and is correlated with SIX1 mRNA upregulation. Collectively, miR-7160 silenced SIX1 and inhibited NSCLC cell growth in vitro and in vivo.