Expression and mechanism of exosome-mediated A FOXM1 related long noncoding RNA in gastric cancer

Abstract

Background Forkhead 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. Results The 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. Conclusion GC 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 registered Graphic abstract

Oncogenic Role of Exosomal Circular and Long Noncoding RNAs in Gastrointestinal Cancers

“…Exosomal FRLnc1 from gastric cancer cells can effectively augment cell proliferation, viability, and migration in receiver cancer cells [123] (Figure 4 and Table 2). Although direct targets of FRLnc1 remain to be identified, FRLnc1 is known to upregulate the level of TGFB1 and TWIST, favoring migration in vitro and lung metastasis in vivo in gastric cancer [180].…”

Potential Biological Roles of Exosomal Long Non-Coding RNAs in Gastrointestinal Cancer

“…Zhang et al found that GC cells treated with the exosomes containing FOXM1-related lncRNA (FRLnc1) can enhance GC cell proliferation and migration. The FRLnc1 knockdown in GC cells can induce cell cycle arrest and cell apoptosis ( Zhang et al, 2021 ). In addition, some studies have shown that the exosomal lncRNAs derived from cancer cells can regulate the cancer immune microenvironment, such as immunosuppressants and immune escape, to promote cancer progression.…”

The Emerging Landscape of Long Non-Coding RNAs in Wilms Tumor

“…Lnc-FRLnc1 is significantly up-regulated in the serum and serum exosomes of patients with gastric cancer. The up-regulation of FRLnc1 expression is closely related to lymph node metastasis and TNM staging ( 71 ). The high expression of Lnc-SCHLAP1 is significantly related to the adverse clinicopathological characteristics of prostate cancer, including grade group, high pT staging, aggressive cribriform growth/prostatic intraductal carcinoma, and reactive stroma ( 72 ).…”