Zhiwei Zhang1, Yang Yang2, Xiuqiang Zhang2. 1. Department of Thoracic Surgery, The Fifth Central Hospital of Tianjin, Tianjin 300450, PR China. Electronic address: zhiweizhang82@126.com. 2. Department of Thoracic Surgery, The Fifth Central Hospital of Tianjin, Tianjin 300450, PR China.
Abstract
AIMS: MicroRNAs (miRNAs) plays important role in development and disease, especially in cancer including non-small cell lung cancer (NSCLC). However, the role of miR-770 in NSCLC remains unclear. In this study, we aimed to study the function and mechanism of miR-770 in tumorigenesis of NSCLC. MAIN METHODS: RT-qPCR was used to measure the expression levels of miR-770 in NSCLC tissues and cells. MTT assay, colony formation assay, flow cytometric analysis and transwell migration and invasion assays were performed to investigate the role of miR-770 in NSCLC cells. Bioinformatics and luciferase reporter analyses were used to demonstrate that whether the Jumonji domain-containing 6 (JMJD6) as a direct target of miR-770. The function of JMJD6 in NSCLC was also investigated. Finally, in vivo animal experiment was used to study whether miR-770 was capable of inhibiting tumor growth by inhibiting JMJD6. KEY FINDINGS: We first showed that miR-770 was downregulated in NSCLC tissues and cell lines, and the low expression of miR-770 was correlated with poor patient survival in NSCLC patients. miR-770 acted on a tumor suppressor by binding to the 3'UTR of JMJD6 and downregulated its expression in NSCLC cells. This study also demonstrated that JMJD6 played as an oncogene in NSCLC cells. miR-770 overexpression was capable of inhibiting NSCLC tumor growth by inhibiting JMJD6 and its downstream WNT/β-catenin pathway both in vitro and in vivo. SIGNIFICANCE: The present study indicated that miR-770 functioned as a tumor suppressor and it might be a potential biomarker and therapeutic target in NSCLC.
AIMS: MicroRNAs (miRNAs) plays important role in development and disease, especially in cancer including non-small cell lung cancer (NSCLC). However, the role of miR-770 in NSCLC remains unclear. In this study, we aimed to study the function and mechanism of miR-770 in tumorigenesis of NSCLC. MAIN METHODS: RT-qPCR was used to measure the expression levels of miR-770 in NSCLC tissues and cells. MTT assay, colony formation assay, flow cytometric analysis and transwell migration and invasion assays were performed to investigate the role of miR-770 in NSCLC cells. Bioinformatics and luciferase reporter analyses were used to demonstrate that whether the Jumonji domain-containing 6 (JMJD6) as a direct target of miR-770. The function of JMJD6 in NSCLC was also investigated. Finally, in vivo animal experiment was used to study whether miR-770 was capable of inhibiting tumor growth by inhibiting JMJD6. KEY FINDINGS: We first showed that miR-770 was downregulated in NSCLC tissues and cell lines, and the low expression of miR-770 was correlated with poor patient survival in NSCLCpatients. miR-770 acted on a tumor suppressor by binding to the 3'UTR of JMJD6 and downregulated its expression in NSCLC cells. This study also demonstrated that JMJD6 played as an oncogene in NSCLC cells. miR-770 overexpression was capable of inhibiting NSCLC tumor growth by inhibiting JMJD6 and its downstream WNT/β-catenin pathway both in vitro and in vivo. SIGNIFICANCE: The present study indicated that miR-770 functioned as a tumor suppressor and it might be a potential biomarker and therapeutic target in NSCLC.
Authors: Tanyeri Barak; Emma Ristori; A Gulhan Ercan-Sencicek; Danielle F Miyagishima; Carol Nelson-Williams; Weilai Dong; Sheng Chih Jin; Andrew Prendergast; William Armero; Octavian Henegariu; E Zeynep Erson-Omay; Akdes Serin Harmancı; Mikhael Guy; Batur Gültekin; Deniz Kilic; Devendra K Rai; Nükte Goc; Stephanie Marie Aguilera; Burcu Gülez; Selin Altinok; Kent Ozcan; Yanki Yarman; Süleyman Coskun; Emily Sempou; Engin Deniz; Jared Hintzen; Andrew Cox; Elena Fomchenko; Su Woong Jung; Ali Kemal Ozturk; Angeliki Louvi; Kaya Bilgüvar; E Sander Connolly; Mustafa K Khokha; Kristopher T Kahle; Katsuhito Yasuno; Richard P Lifton; Ketu Mishra-Gorur; Stefania Nicoli; Murat Günel Journal: Nat Med Date: 2021-12-09 Impact factor: 87.241