生物
PI3K/AKT/mTOR通路
癌症研究
蛋白激酶B
小核仁RNA
癌变
癌基因
AKT2型
蛋白磷酸酶2
信号转导
长非编码RNA
细胞生物学
细胞周期
细胞生长
癌症
磷酸化
下调和上调
AKT1型
磷酸酶
遗传学
基因
作者
Baoqing Tian,Jiandong Liu,Nasha Zhang,Yemei Song,Yeyang Xu,Mengyu Xie,Bowen Wang,Hui Hua,Yue Shen,Yankang Li,Ming Yang
出处
期刊:Oncogene
[Springer Nature]
日期:2021-05-01
卷期号:40 (21): 3734-3747
被引量:13
标识
DOI:10.1038/s41388-021-01809-2
摘要
Esophageal cancer is a complex malignancy and the sixth leading cause of cancer death worldwide. In Eastern Asia including China, about 90% of all incident cases have esophageal squamous cell carcinoma (ESCC). Mounting evidence elucidates that aberrant expression of various non-coding RNAs (ncRNAs) contributes to ESCC progression, but it remains unclear how small nucleolar RNAs (snoRNAs) are involved in ESCC development. We systemically screened clinically relevant snoRNAs in ESCC via integrative analyses of The Cancer Genome Atlas (TCGA) data and validation in ESCC tissues. We found that snoRNA SNORD12B was one of the most evidently upregulated snoRNAs in ESCC specimens and its high expression was significantly associated with poor prognosis of patients. SNORD12B profoundly promoted proliferation, migration, invasion, and metastasis of ESCC cells in vitro and in vivo, indicating its oncogene nature. In particular, SNORD12B could interact with PP-1α, one of the three catalytic subunits of serine/threonine protein phosphatase 1, which is a major phosphatase that directly dephosphorylates AKT to suppress its activation. Interestingly, high levels of SNORD12B in ESCC cells could break interactions between 14-3-3ζ and PP-1α, abolish the retention of PP-1α in the cytosol by 14-3-3ζ and relocate PP-1α from the cytosol to the nucleus. This led to sequestered PP-1α in the nucleus, enhanced phosphorylation of AKT in the cytosol, activated AKT-mTOR-4EBP1 signaling, and, thus, ESCC progression. These insights would improve our understanding of how snoRNAs contribute to tumorigenesis and highlight the potential of snoRNAs as future therapeutic targets against cancers.
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