Abstract
BackgroundForkhead box protein M1 (FOXM1) is an oncogene regulating tumor growth and metastasis. Exosome was suggested to mediate cell communication by delivering active molecules in cancers. However, the existence of FOXM1 in circulating exosomes and the role of exosome FOXM1 in gastric cancer (GC) were not clear. This study aims to investigate the potential role of FOXM1 related long noncoding RNA (FRLnc1) in exosomes in GC.ResultsThe prepared CD63 immunomagnetic beads (CD63-IMB) had the characteristics of good dispersity and high magnetic response. The isolated exosomes were presented with elliptical membranous particles under a transmission electron microscope (TEM), with the particle size of 89.78 ± 4.8 nm. Western blot (WB) results showed that the exosomes were rich in CD9 and CD81. The Dil-labeled exosomes were distributed around cytoplasm and nucleus of cells by imaging flow cytometry (IFC) analysis. The results of quantitative real-time PCR (qRT-PCR) revealed that the FRLnc1 expressions were up-regulated in GC cells, tumor tissues, and serum of GC patients. An obviously up-regulated FRLnc1 expression was found in serum exosomes of GC patients. Up-regulation of FRLnc1 expression was closely correlated to lymph node metastasis (LNM) and TNM stage with the combination of relevant clinicopathological parameter analysis. The in vitro functional analyses demonstrated that FRLnc1 knockdown by RNA interference suppressed cell proliferation and migration in HGC-27 cells, whereas FRLnc1 overexpression promoted cell proliferation and migration in MKN45 cells. After exosome treatment, the FRLnc1 expression was significantly increased in MKN45 cells, and the MKN45 cells showed increased ability of proliferation and migration.ConclusionGC cells-derived exosomes played roles in promoting the growth and metastasis of GC by transporting FRLnc1, suggesting that FRLnc1 in the exosomes may be a potential biomarker for the diagnosis and treatment of GC. The delivery of FRLnc1 by the exosomes may provide a new way for the treatment of GC.Trial registration 2020-KYSB-094. Registered 23 March 2020—Retrospectively registeredGraphic abstract
Highlights
Forkhead box protein M1 (FOXM1) is an oncogene regulating tumor growth and metastasis
CD63-immunomagnetic beads (IMB) FT-IR spectra, new peaks appeared at approximately 2840–2930 cm−1, these peaks were attributed to the long carbon chain and methyl groups on the quaternary ammonium salt, representing the existence of glycero3-phosphocholine (DOPC) and dimethyloctadecylepoxypropane-ammonium chloride (GHDC) on the CD63-GHDC and CD63-IMB
Pan et al [31] found that ZFAS1 was highly expressed in serum exosomes of gastric cancer (GC) patients, and the expression level of ZFAS1 was significantly correlated to lymph node metastasis (LNM) and TNM stage, and ROC curve showed that AUC was 0.837, with the sensitivity being 80.00% and the specificity being 75.7%, indicating that the exosomes could promote the malignant progress of GC by transporting ZFAS1
Summary
Forkhead box protein M1 (FOXM1) is an oncogene regulating tumor growth and metastasis. The existence of FOXM1 in circulating exosomes and the role of exosome FOXM1 in gastric cancer (GC) were not clear. This study aims to investigate the potential role of FOXM1 related long noncoding RNA (FRLnc1) in exosomes in GC. Gastric cancer (GC) is a highly heterogeneous disease. It is the second leading cause of cancer death in the world. It is a common gastrointestinal malignant tumor and ranks the fourth cause of death of malignant tumors [1]. It was reported that the lack of appropriate molecular biomarkers was one of the main reasons for the low overall survival rate of GC patients, as a result, without effectively early diagnosis, most GC patients missed the best opportunity for surgical treatment [4]. The discovery of a new specific biomarker was of great significance for the early diagnosis, prognosis evaluation and treatment of GC
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