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Abstract
BackgroundExosomes are vesicles of endocytic origin released by various cell types and emerging as important mediators in tumor cells. Human metastases-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA known to promote cell proliferation, metastasis, and invasion in colorectal cancer (CRC).MethodsThe expression of MALAT1 was analyzed in CRC using qRT-PCR. FUT4 and fucosylation levels were detected in CRC clinical samples and CRC cell lines by immunofluorescent staining, western blot and lectin blot analysis. CRC derived exosomes were isolated and used to examine their tumor-promoting effects in vitro and in vivo.ResultsThe invasive and metastatic abilities of primary CRC cells were enhanced after exposure to exosomes derived from highly metastatic CRC cells, which increased the fucosyltransferase 4 (FUT4) levels and fucosylation not by directly transmitting FUT4 mRNA. Exosomal MALAT1 increased FUT4 expresssion via sponging miR-26a/26b. Furthermore, MALAT1/miR-26a/26b/FUT4 axis played an important role in exosome-mediated CRC progression. Exosomal MALAT1 also mediated FUT4-associated fucosylation and activated the PI3K/AKT/mTOR pathway.ConclusionsThese data indicated that exosomal MALAT1 promoted the malignant behavior of CRC cells by sponging miR-26a/26b via regulating FUT4 and activating PI3K/Akt/mTOR pathway.
Highlights
Exosomes are vesicles of endocytic origin released by various cell types and emerging as important mediators in tumor cells
Our findings provide further evidence that exosomal metastases-associated lung adenocarcinoma transcript 1 (MALAT1) contributes to colorectal cancer (CRC) progression and regulates fucosyltransferase 4 (FUT4) expression by sponging miR-26a/26b via fucosylation and Phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which may provide novel insights into the function of exosomal MALAT1 in CRC
Nude mice were anaesthetized with pentobarbital sodium (Sigma, USA) by intraperitoneal injection. 1 cm Metastatic CRC cell-derived exosomes were transferred to primary CRC cells and increased malignant traits of primary CRC cells in vitro and in vivo We first examined whether CRC cells secreted exosomes
Summary
Exosomes are vesicles of endocytic origin released by various cell types and emerging as important mediators in tumor cells. To the Exosomes, membrane vesicles of endocytic origin ranging in size from 30 to 150 nm approximately, are emerging as key players in intercellular communication between cancer cells and their microenvironment [5]. Exosomes are described as functional mediator of cancerous malignant alteration in recipient cells [8]. This intercellular communication is known to be involved in various pathophysiological processes including cell proliferation, migration, apoptosis, treatment resistance and metastasis [9,10,11,12], tumor innervation [13] and angiogenesis [14]. It is important to explore the mechanisms by which exosomes derived from CRC cells regulate CRC progression, especially the metastatic process
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