miRNA-425-5p enhances lung cancer growth via the PTEN/PI3K/AKT signaling axis
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RESEARCH ARTICLE
Open Access
miRNA-425-5p enhances lung cancer growth via the PTEN/PI3K/AKT signaling axis Jin-shan Zhou, Ze-shan Yang, Si-yang Cheng, Jiang-hao Yu, Chao-Jun Huang and Qiang Feng*
Abstract Background: miRNAs regulate a multitude of cellular processes and their aberrant regulation is linked to human cancer. However, the role of miR-425-5p in lung cancer (LCa) is still largely unclear. Here, we explored the role of miR-425-5p during LCa tumorigenesis. Methods: Cell proliferation was evaluated by cell counting Kit-8 and colony formation assay. Western blot and realtime PCR were accordingly used to detect the relevant proteins, miRNA and gene expression. Luciferase reporter assays were used to illustrate the interaction between miR-425-5p and PTEN. Results: We demonstrate that miR-425-5p is overexpressed in LCa tissue and enhances the proliferative and colony formation capacity of the LCa cell lines A549 and NCI-H1299. Through predictive binding assays, PTEN was identified as a direct gene target and its exogenous expression inhibited the pro-cancer effects of miR-425-5p. Through its ability to down-regulate PTEN, miR-425-5p activated the PI3K/AKT axis. Conclusion: We conclude that miR-425-5p promotes LCa tumorigenesis through PTEN/PI3K/AKT signaling. Keywords: miR-425-5p, Lung cancer, PTEN, PI3K/AKT signaling pathways
Background Lung cancer (LCa) is a leading cause of cancer related mortality across the globe. LCa is prevalent in males [1] and asymptomatic during early disease stages. As many as 2 in every 3 cases are at an advanced stage (III or IV) when diagnosed and the 5-year survival rates remain low, particularly for those with metastatic LCa [2]. Improved LCa therapeutics is thus urgently required. MicroRNAs (miRNAs) regulate many cell processes including differentiation, metabolism and tumorigenesis [3–6]. Emerging evidence suggests that miRNAs are key players during LCa tumorigenesis [7–10]. The aberrant expression of miR-425-5p is linked to hepatocellular carcinoma (HCC), gastric cancer (GCa) and colorectal * Correspondence: [email protected] Cardiothoracic Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Shangchen Road NO.1 of Yiwu, Zhejiang 322000, China
cancer (CRC) [11–13]. Here, we report the upregulation of miR-425-5p in LCa and highlight its contribution to LCa development. We further identify PTEN as a novel miR-425-5p target that is inhibited in LCa to promote PTEN/PI3K/AKT signaling.
Methods Patient specimens
LCa samples (n = 25) and adjacent healthy tissue (at least 2 cm from the resection margin) were collected from the Fourth Affiliated Hospital, Zhejiang University School of Medicine. The study was fully supported by the Institutional Review Board of the Fourth Affiliated Hospital, Zhejiang University School of Medicine (No.2015-0-09). All participants provided consent for sample analysis and anything about their identities will not be included in the data.
© The Author(s). 2020 Open Access This article is licensed under a Creative Commons At
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