BackgroundLong non-coding RNAs (LncRNAs) emerging as pivotal marker in the procession of cancer, including colorectal cancer (CRC). Abnormal O-glycosylation is a crucial modification during cancer malignancy. The aim of this work is to analyze the alteration of O-glycosylation involved in CRC progression.MethodsqRT-PCR is utilized to screen the differential linc01296 expression in CRC tissues and cell lines. Functionally, CRC cell proliferation, aggressiveness and apoptosis are measured through relevant experiments, including CCK8 assay, colony formation assay, transwell assay, western blot and flow cytometry. Dual-luciferase reporter gene assay and RIP assay confirm the direct interaction between linc01296 and miR-26a. The xenografts and liver metatstatic nude mice models are established to show the inner effect of linc01296.ResultsDifferential expression of linc01296 is confirmed and closely correlated with the malignancy of CRC cell lines and poor clinical prognosis. Moreover, alteration of linc01296 affects CRC cell proliferation, metastasis and chemoresistance to 5-fluorouracil (5-FU) in vitro. Mechanically, linc01296 acts as a direct target of miR-26a, and thereby influenced CRC malignancy. Our investigation corroborates that linc01296 functions as an endogenous sponge of miR-26a to regulate mucin1 (MUC1) expression, catalyzed by GALNT3, which modulates the activity of PI3K/AKT pathway. Interestingly, upregulated linc01296 promotes the tumorigensis, liver metastasis and chemoresistance of CRC cell lines in vivo.ConclusionThese new findings indicate that linc01296/miR-26a/GALNT3 axis involves in the progression of CRC cells, illuminating the possible mechanism mediated by O-glycosylated MUC1 via PI3K/AKT pathway. This work renders potential diagnostic biomarkers and prospective therapeutic targets for CRC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0994-x) contains supplementary material, which is available to authorized users.

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

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Drug-resistance is a major problem in acute myeloid leukemia (AML) chemotherapy. Aberrant changes in specific N-glycans have been observed in leukemia multidrug resistance (MDR). MicroRNAs (miRNAs) and long non coding RNAs (lncRNAs) act as key players in the development of AML resistance to chemotherapy. In the present study, the N-glycan profiles of membrane proteins were analyzed from adriamycin (ADR)-resistant U937/ADR cells and sensitive line U937 cells using mass spectrometry (MS). The composition profiling of high-mannose N-glycans differed in U937/ADR and U937 cell lines. Lectin microarray showed that the strong binding of membrane proteins was observed for MAN-M and ConA lectins, which were specific for mannose. These binding were also validated by flow cytometry. Importantly, the alteration of high-mannose N-glycan was further confirmed by detecting the enzyme level of ALG family. The altered level of ALG3 was found corresponding to the drug-resistant phenotype of AML cell lines both in vitro and in vivo. Mechanistically, miR-342 was found to be dysregulated and inversely correlated to ALG3 expression, targeting its 3′-UTR. LncRNA FTX was a direct target of miR-342 and positively modulated ALG3 expression by competitively binding miR-342 in AML cell lines. Functionally, we found that FTX directly interacted with miR-342 to regulate ALG3 expression and function, including ADR-resistant cell growth and apoptosis. The observation suggested that high-mannose N-glycans and mannosyltransferase ALG3 affected drug-resistance in AML cells. FTX/miR-342/ALG3 axis could potentially be used for the targets to overcome therapeutic resistance in AML.

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