HOTAIR/miR-326/FUT6 axis facilitates colorectal cancer progression through regulating fucosylation of CD44 via PI3K/AKT/mTOR pathway

Publication date: Available online 8 February 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Shimeng Pan, Yanqiu Liu, Qianqian Liu, Yang Xiao, Bing Liu, Xiang Ren, Xia Qi, Huimin Zhou, Changqian Zeng, Li JiaAbstractMetastasis is the main cause of death in colorectal cancer (CRC) patients. Aberrant fucosylation, catalyzed by the specific fucosyltransferases (FUTs), is associated with malignant behaviors. Non-conding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), emerge as key molecules in cancer malignancy. The aim of this study was to investigate HOTAIR/miR-326/FUT6 axis modified fucosylation on sLeX-CD44 (HCELL), which served as E-selectin ligand during CRC progression. Higher levels of HOTAIR and FUT6 were verified in CRC tissues and cell lines, with a positive correlation. HOTAIR was associated with poor clinical prognosis of CRC. Altered HOTAIR levels influenced proliferation, aggressiveness, apoptosis and tumorigenesis of CRC cells. HOTAIR directly harbored miR-326 binding sites and regulated FUT6 expression. Further results corroborated that HOTAIR/miR-326/FUT6 axis modified α1, 3-fucosylation of CD44, which mediated CRC malignancy. Co-modulation of HOTAIR, miR-326 and FUT6 impacted α1, 3-fucosylated CD44, which further triggered PI3K/AKT/mTOR pathway. HOTAIR also mediated CRC tumorigenesis and liver metastasis in vivo. Thus, our findings indicated that HOTAIR/miR-326/FUT6 axis mediated CRC procession throug...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research