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LncRNA ST3Gal6‐AS1/ST3Gal6 axis mediates colorectal cancer progression by regulating α‐2,3 sialylation via PI3K/Akt signaling
Author(s) -
Hu Jialei,
Shan Yujia,
Ma Jia,
Pan Yue,
Zhou Huimin,
Jiang Liqun,
Jia Li
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32103
Subject(s) - cancer research , metastasis , carcinogenesis , colorectal cancer , protein kinase b , biology , pi3k/akt/mtor pathway , tumor progression , cell growth , transcription factor , signal transduction , cancer , microbiology and biotechnology , genetics , gene
Sialylation is associated with cancer progression. Long noncoding RNAs (lncRNAs) have important roles in diverse diseases including cancer. The lncRNA ST3Gal6 antisense 1 (ST3Gal6‐AS1) derives from the promoter region of sialyltransferase ST3Gal6. However, the mechanisms by which ST3Gal6‐AS1 modulates colorectal cancer (CRC) development through sialylation remain largely unknown. Here, we found that ST3Gal6‐AS1 and ST3Gal6 levels were lower in tumor tissues than adjacent normal tissues of CRC patients. The correlation between ST3Gal6‐AS1 and ST3Gal6 was further validated in several types of CRC cell lines. In addition, ST3Gal6 was dysregulated and positively correlated to ST3Gal6‐AS1. ST3Gal6‐AS1 recruited histone methyltransferase MLL1 to the promoter region of ST3Gal6, induced H3K4me3 modification and activated ST3Gal6 transcription. Furthermore, ST3Gal6‐AS1/ST3Gal6 axis mediated α‐2, 3 sialylation and inhibited the activation of PI3K/Akt signaling, thereby resulting in Foxo1 nuclear translocation in CRC cells. ST3Gal6‐AS1 was a target of transcription factor Foxo1 and regulated by Foxo1. ST3Gal6‐AS1 also inhibited CRC cell proliferation, metastasis, and promoted cell apoptosis in vitro . Overexpression of ST3Gal6‐AS1 significantly decreased the tumorigenesis, lung and liver metastasis of SW620 cells in vivo . ST3Gal6‐AS1 expression was negatively correlated with tumor size, lymphatic metastasis, distant metastasis and tumor stage in CRC patients. Collectively, these data indicated that ST3Gal6‐AS1, ST3Gal6, PI3K/Akt, and Foxo1 formed a positive feedback loop, which might play a key role in CRC progression.