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

Abstract

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.

LUCAT1 contributes to MYRF‐dependent smooth muscle cell apoptosis and may facilitate aneurysm formation via the sequestration of miR‐199a‐5p

“…LncRNAs was disease‐related through a host of mechanisms such as chromatin modification, transcription, and post‐transcriptional processing (Zhang et al, ), among which miRNA‐like sponge suggested that lncRNA bind to and inhibit miRNAs and therefore control the post‐transcriptional regulation of miRNA on target gene expression (Tay et al, ). For example, LINC01296/miR‐26a/GALNT3 axis contributes to colorectal cancer progression by regulating O ‐glycosylated MUC1 via PI3K/AKT pathway (Liu et al, ). LncRNA‐TUSC7/miR‐224 affected chemotherapy resistance of esophageal squamous cell carcinoma by competitively regulating DESC1 (Chang et al, ).…”

Overexpression of TC2N is associated with poor prognosis in gastric cancer

“…In this study, we also demonstrated that TC2N overexpression was signi cantly related to the clinicopathological features in GC and promoted the its development in vitro. Bioinformatic analysis suggested a connection between TC2N and a series of genes related to human cancer and other diseases, such as CATSPERB, a novel transmembrane protein playing role in the eld of reproduction [34], GALNT3, proved to play important roles in different cancers [35][36][37] and RBM47, reported to inhibit tumor progression in lung, breast and colon cancer [38][39][40]. These evidences further veri ed the potential role of TC2N in GC from another aspect.…”

Prognostic value of long non-coding RNA 01296 expression in human solid malignant tumours: a meta-analysis

“…As mentioned above, an electronic database search identified 113 literatures according to the search strategy. After a full assessment of these researches, a total of 11 articles21–26 28 31–34 that reported the possible functions or pathways of LINC01296 in human solid malignant tumours were included. Following a summary of the functions and pathways of LINC01296 among the articles, we showed a concise overview of the functionality of LINC01296 in figure 6.…”