EVI5 is an oncogene that regulates the proliferation and metastasis of NSCLC cells

Abstract

Background: The Ecotropic viral integration site 5 (EVI5), an important protein in regulating cell cycle, cytokinesis and cellular membrane traffic, functions as a stabilizing factor maintaining anaphase-promoting complex/cyclosome (APC/C) inhibitor Emi1 in S/G2 phase. However, the mechanism by which EVI5 promotes malignant transformation of non-small cell lung cancer (NSCLC) remains unknown. In the present study, we addressed the role of EVI5 in NSCLC by regulating tumor growth, migration and invasion. Methods: The expression levels of EVI5 and miR-486-5p in NSCLC tissues and cells were measured by real-time PCR. Meanwhile, EVI5 and its associated protein expression were analyzed by western blot and coimmunoprecipitation assay. Flow cytometry was performed to determine cell proliferation and apoptosis. CCK-8 and clonogenic assays were used to analyze cell viability. Wound healing, transwell migration and matrigel invasion assays were utilized to assess the motility of tumor cells. To investigate the role of EVI5 in vivo, lung carcinoma xenograft mouse model was applied.. Results: EVI5 was upregulated in NSCLC tissues and cell lines when compared with that in normal tissues and cell line. Knockdown of EVI5 in vitro inhibited tumor cell proliferation, migration and invasion in NSCLC cells. Further, inoculation of EVI5-deficient tumor cells into nude mice suppressed tumor proliferation and metastasis compared to control mice inoculated with unmanipulated tumor cells. These data indicated that EVI5 promote the proliferation of NSCLC cells which was consistent with our previous results. Additionally, we showed that EVI5 was directly regulated by miR-486-5p, and miR-486-5p-EVI5 axis affected the NSCLC migration and invasion through TGF-β/Smad signaling pathway by interacting with TGF-β receptor II and TGF-β receptor I. Conclusions: Based on these results, we demonstrated a new post-transcriptional mechanism of EVI5 regulation via miR-486-5p and the protumoral function of EVI5 in NSCLC by interacting with Emi1 and/or TGF-β receptors, which provides a new insight into the targeted therapy of NSCLC.

Fucosylated exosomal miRNAs as promising biomarkers for the diagnosis of early lung adenocarcinoma

“…Interestingly, our previous study also showed that the expression level of serum exosomal hsamir-486-5p in early NSCLC was significantly upregulated, which presents good diagnostic value for patients with early NSCLC (39). Moreover, it was reported that the EVI5 oncogene was directly regulated by hsa-mir-486-5p, and hsa-mir-486-5p-EVI5 axis affected the NSCLC migration and invasion through the TGF-b/ Smad signaling pathway (40). hsa-miR-451a has also been shown to have an association with lung cancer.…”

Identification of diagnostic biomarkers for idiopathic pulmonary hypertension with metabolic syndrome by bioinformatics and machine learning

“…EVI5 has different regulatory roles in cell cycle progression, cytokinesis, and cell membrane trafficking. In tumors, EVI5 expression is dysregulated in multiple cancer types, such as non-small-cell lung cancer, laryngeal cancer, and hepatocellular carcinoma, and EVI5 is therefore considered potential oncogenes and cell-cycle regulators [25][26][27] . EVI5 is also a risk factor for multiple sclerosis 28 .…”

Inhibition of ox‐LDL‐induced endothelial cell injury by LINC02381 knockdown through the microRNA‐491‐5p/transcription factor 7 axis

“…At 0, 24, 48, and 72 h, 10 μL of Cell Counting Kit‐8 solution was supplemented into each well and incubated for another 2 h at room temperature. Eventually, an enzyme marker was used to measure the sample absorbances 32 …”