LncRNA MYLK-AS1 facilitates tumor progression and angiogenesis by targeting miR-424-5p/E2F7 axis and activating VEGFR-2
- PDF / 8,605,733 Bytes
- 18 Pages / 595.276 x 790.866 pts Page_size
- 30 Downloads / 186 Views
RESEARCH
(2020) 39:235
Open Access
LncRNA MYLK-AS1 facilitates tumor progression and angiogenesis by targeting miR-424-5p/E2F7 axis and activating VEGF R-2 signaling pathway in hepatocellular carcinoma Fei Teng1,2†, Ju-Xiang Zhang3†, Qi-Meng Chang1,2, Xu-Bo Wu1,2, Wei-Guo Tang1,2, Jian-Fa Wang1,2, Jin-Feng Feng1,2, Zi-Ping Zhang1,2* and Zhi-Qiu Hu1,2*
Abstract Background: Long non-coding RNAs (lncRNAs) are crucial in the invasion, angiogenesis, progression, and metastasis of hepatocellular carcinoma (HCC). The lncRNA MYLK-AS1 promotes the growth and invasion of HCC through the EGFR/HER2-ERK1/2 signaling pathway. However, the clinical significance of MYLK-AS1 in HCC still needs to be further determined. Methods: Bioinformatic analysis was performed to determine the potential relationship among MYLK-AS1, miRNAs and mRNAs. A total of 156 samples of normal liver and paired HCC tissues from HCC patients were used to evaluate MYLKAS1 expression by qRT-PCR. Human HCC cell lines were used to evaluate the colony formation, cell proliferation, migration, invasion, cell cycle and apoptosis after transfection of lentiviral short-hairpin RNAs (shRNAs) targeting MYLKAS1 or MYLK-AS1 vectors. The competitive endogenous RNA (ceRNA) mechanism was clarified using fluorescence in situ hybridization (FISH), Western blotting, qPCR, RNA binding protein immunoprecipitation (RIP), and dual luciferase reporter analysis. Results: MYLK-AS1 up-regulation was detected in the HCC tumor tissues and cell lines associated with the enhancement of the angiogenesis and tumor progression. The down-regulation of MYLK-AS1 reversed the effects on angiogenesis, proliferation, invasion and metastasis in the HCC cells and in vivo. MYLK-AS1 acted as ceRNA, capable of regulating the angiogenesis in HCC, while the microRNA miR-424-5p was the direct target of MYLK-AS1. Promoting the angiogenesis and the tumor proliferation, the complex MYLK-AS1/miR-424-5p activated the VEGFR-2 signaling through E2F7, whereas the specific targeting of E2F transcription factor 7 (E2F7) by miR-424-5p, was indicated by the mechanism studies. (Continued on next page)
* Correspondence: [email protected]; [email protected] † Fei Teng and Ju-Xiang Zhang contributed equally to this work. 1 Department of Hepatobiliary and Pancreatic Surgery, Minhang Hospital, Fudan University, Shanghai 201199, People’s Republic of China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's
Data Loading...
