STAT5A modulates CDYL2/SLC7A6 pathway to inhibit the proliferation and invasion of hepatocellular carcinoma by targeting to mTORC1 View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2022-03-21

AUTHORS

Xiaoxia Chen, Zhenyu Wang, Xinge Zhao, Lili Zhang, Lianer Zhou, Xianxian Li, Chao Ge, Fangyu Zhao, Taoyang Chen, Haiyang Xie, Ying Cui, Hua Tian, Hong Li, Ming Yao, Jinjun Li

ABSTRACT

Chromodomain Y-like 2 (CDYL2), as a member of CDY family known to be involved in spermatogenesis, has been reported to participate in breast cancer development recently, but its exact biological role in hepatocellular carcinoma (HCC) remains unclear. Here, we observed that CDYL2 was down-regulated in human primary HCC tissues and the low levels of CDYL2 expression were correlated with poor survival. Gain- and loss-of-function experiments showed that CDYL2 inhibited the proliferation and metastasis of HCC cells in vitro and in vivo. Mechanistically, CDYL2 down-regulates solute carrier family 7 member 6 (SLC7A6) by decreasing the enrichment of H3K4me3 on the promoter region of SLC7A6. Additionally, we also found that signal transducer and activator of transcription 5A (STAT5A) could directly and positively regulate the expression of CDYL2. Thus, CDYL2 was regulated by STAT5A, and suppressed the amino acid transportation through down-regulation of SLC7A6, and then inhibits the mTORC1/S6K pathway, a master regulator of cell growth. Consistently, CDYL2 expression correlated significantly with STAT5A and SLC7A6 expression in HCC. Collectively, we propose a model for a STAT5A/CDYL2/SLC7A6 axis that provides novel insight into CDYL2, which may serve as a potential factor for predicting prognosis and a therapeutic target for HCC patients. More... »

PAGES

2492-2504

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41388-022-02273-2

DOI

http://dx.doi.org/10.1038/s41388-022-02273-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1146456887

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35314791


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38 amino acid transportation
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52 expression
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56 growth
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58 human primary HCC tissues
59 insights
60 invasion
61 levels
62 loss
63 low levels
64 master regulator
65 member 6
66 members
67 metastasis
68 model
69 novel insights
70 pathway
71 patients
72 poor survival
73 potential factors
74 primary HCC tissues
75 prognosis
76 proliferation
77 promoter region
78 region
79 regulator
80 role
81 signal transducer
82 spermatogenesis
83 survival
84 target
85 therapeutic target
86 tissue
87 transcription 5A
88 transducer
89 transportation
90 vitro
91 vivo
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