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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Research

LINC01296/miR-26a/GALNT3 axis contributes to colorectal cancer progression by regulating O-glycosylated MUC1 via PI3K/AKT pathway

Authors: Bing Liu, Shimeng Pan, Yang Xiao, Qianqian Liu, Jingchao Xu, Li Jia

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

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Abstract

Background

Long 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.

Methods

qRT-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.

Results

Differential 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.

Conclusion

These 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.
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Metadata
Title
LINC01296/miR-26a/GALNT3 axis contributes to colorectal cancer progression by regulating O-glycosylated MUC1 via PI3K/AKT pathway
Authors
Bing Liu
Shimeng Pan
Yang Xiao
Qianqian Liu
Jingchao Xu
Li Jia
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0994-x

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