Background: Exosomes 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 noncoding RNA known to promote cell proliferation, metastasis, and invasion in colorectal cancer (CRC).Methods: The 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.
Results:The 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.Conclusions: These 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.Keywords: CRC, Exosomal MALAT1, FUT4, miR-26a/26b, PI3K/Akt/mTOR pathway Background Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality [1,2]. More than 60% of CRC patients have initiated the metastatic process by the time of diagnosis [3]. Although there are multiple tests available for CRC screening, each method has its own limitations in terms of sensitivity and specificity. To the best of our knowledge, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are well established tumor markers with low sensitivity and specificity for early detection of CRC [4]. Hence, ideal CRC-specific biomarkers are urgently required to improve the current CRC diagnostic strategies.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]. A distinct feature of exosomes is that they efficiently carry and deliver molecular signatures (proteins, lipids, RNA