HBXIP-elevated methyltransferase METTL3 promotes the progression of breast cancer via inhibiting tumor suppressor let-7g

被引:390
作者
Cai, Xiaoli [1 ]
Wang, Xiao [1 ]
Cao, Can [1 ]
Gao, Yuen [2 ]
Zhang, Shuqin [2 ]
Yang, Zhe [2 ]
Liu, Yunxia [2 ]
Zhang, Xiaodong [2 ]
Zhang, Weiying [1 ]
Ye, Lihong [1 ]
机构
[1] Nankai Univ, Coll Life Sci, Dept Biochem, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China
[2] Nankai Univ, Coll Life Sci, Dept Canc Res, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China
基金
中国国家自然科学基金;
关键词
HBXIP; METTL3; let-7g; Proliferation; Breast cancer; MESSENGER-RNA METHYLATION; SELF-RENEWAL; ONCOPROTEIN; M(6)A; PROLIFERATION; GROWTH; CELLS; DEMETHYLASE; MICRORNAS; ALKBH5;
D O I
10.1016/j.canlet.2017.11.018
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Methyltransferase-like 3 (METTL3) is involved in RNA metabolism through N6-methyladenosine (m6A) modification. However, whether METTL3 participates in the progression of breast cancer is unclear. Aberrant expression of Mammalian hepatitis B X-interacting protein (HBXIP) drives the aggressiveness of breast cancer. Here, we are interested in the potential links between HBXIP and METTL3 in breast cancer. We showed that the expression of METTL3 was positively related to that of HBXIP in clinical breast cancer tissues. Moreover, HBXIP could up-regulate METTL3 in breast cancer cells. Mechanistically, HBXIP modulated METTL3 by inhibiting miRNA let-7g, which down-regulated the expression of METTL3 by targeting its 3'UTR. Strikingly, we found that METTL3 promoted the expression of HBXIP through m6A modification. Furthermore, overexpressed HBXIP could rescue the inhibited-proliferation and enhanced-apoptosis induced by silencing of METTL3 in breast cancer cells. Thus, we conclude that HBXIP up regulates METTL3 by suppressing let-7g, in which METTL3 increased HBXIP expression forming a positive feedback loop of HBXIP/let-7g/METTL3/HBXIP, leading to accelerated cell proliferation in breast cancer. Our finding provides new insights into the mechanism of the mutual regulation between HBXIP and METTL3 in the progression of breast cancer. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码:11 / 19
页数:9
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