Published on Feb. 28, 2018 in Cancer Lett volume 415DP - 2018 Feb 28TI - HBXIP-elevated methyltransferase METTL3 promotes the progression of breast cancervia inhibiting tumor suppressor let-7g.PG - 11-19LID - S0304-3835(17)30740-1 [pii]LID - 10.1016/j.canlet.2017.11.018 [doi]AB - Methyltransferase-like 3 (METTL3) is involved in RNA metabolism throughN6-methyladenosine (m(6)A) modification. However, whether METTL3 participates in theprogression of breast cancer is unclear. Aberrant expression of Mammalian hepatitisB X-interacting protein (HBXIP) drives the aggressiveness of breast cancer. Here, weare interested in the potential links between HBXIP and METTL3 in breast cancer. Weshowed that the expression of METTL3 was positively related to that of HBXIP inclinical breast cancer tissues. Moreover, HBXIP could up-regulate METTL3 in breastcancer cells. Mechanistically, HBXIP modulated METTL3 by inhibiting miRNA let-7g,which down-regulated the expression of METTL3 by targeting its 3'UTR. Strikingly, wefound that METTL3 promoted the expression of HBXIP through m(6)A modification.Furthermore, overexpressed HBXIP could rescue the inhibited-proliferation andenhanced-apoptosis induced by silencing of METTL3 in breast cancer cells. Thus, weconclude that HBXIP up-regulates METTL3 by suppressing let-7g, in which METTL3increased HBXIP expression forming a positive feedback loop ofHBXIP/let-7g/METTL3/HBXIP, leading to accelerated cell proliferation in breastcancer. Our finding provides new insights into the mechanism of the mutualregulation between HBXIP and METTL3 in the progression of breast cancer.CI - Copyright © 2017 Elsevier B.V. All rights reserved.FAU - Cai, XiaoliAU - Cai XAD - State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry,College of Life Sciences, Nankai University, Tianjin 300071, China.FAU - Wang, XiaoAU - Wang XAD - State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry,College of Life Sciences, Nankai University, Tianjin 300071, China.FAU - Cao, CanAU - Cao CAD - State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry,College of Life Sciences, Nankai University, Tianjin 300071, China.FAU - Gao, YuenAU - Gao YAD - State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research,College of Life Sciences, Nankai University, Tianjin 300071, China.FAU - Zhang, ShuqinAU - Zhang SAD - State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research,College of Life Sciences, Nankai University, Tianjin 300071, China.FAU - Yang, ZheAU - Yang ZAD - State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research,College of Life Sciences, Nankai University, Tianjin 300071, China.FAU - Liu, YunxiaAU - Liu YAD - State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research,College of Life Sciences, Nankai University, Tianjin 300071, China.FAU - Zhang, XiaodongAU - Zhang XAD - State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research,College of Life Sciences, Nankai University, Tianjin 300071, China.FAU - Zhang, WeiyingAU - Zhang WAD - State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry,College of Life Sciences, Nankai University, Tianjin 300071, China. Electronicaddress: zhwybao@nankai.edu.cn.FAU - Ye, LihongAU - Ye LAD - State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry,College of Life Sciences, Nankai University, Tianjin 300071, China. Electronicaddress: yelihong@nankai.edu.cn.LA - engPT - Journal ArticlePT - Research Support, Non-U.S. Gov'tDEP - 20171122PL - IrelandTA - Cancer LettJT - Cancer lettersJID - 7600053RN - 0 (3' Untranslated Regions)RN - 0 (Adaptor Proteins, Signal Transducing)RN - 0 (LAMTOR5 protein, human)RN - 0 (MicroRNAs)RN - 0 (mirnlet7 microRNA, human)RN - EC 2.1.1.- (Methyltransferases)RN - EC 2.1.1.62 (METTL3 protein, human)SB - IMMH - 3' Untranslated Regions/geneticsMH - Adaptor Proteins, Signal Transducing/*genetics/metabolismMH - AdultMH - AgedMH - Base SequenceMH - Breast Neoplasms/*genetics/metabolism/pathologyMH - Disease ProgressionMH - FemaleMH - *Gene Expression Regulation, NeoplasticMH - Genes, Tumor SuppressorMH - HumansMH - MCF-7 CellsMH - Methyltransferases/*genetics/metabolismMH - MicroRNAs/*geneticsMH - Middle AgedMH - Sequence Homology, Nucleic AcidMH - Young AdultOTO - NOTNLMOT - *Breast cancerOT - *HBXIPOT - *METTL3OT - *ProliferationOT - *let-7gEDAT- 2017/11/28 06:00MHDA- 2018/10/23 06:00CRDT- 2017/11/28 06:00PHST- 2017/08/14 00:00 [received]PHST- 2017/10/30 00:00 [revised]PHST- 2017/11/17 00:00 [accepted]PHST- 2017/11/28 06:00 [pubmed]PHST- 2018/10/23 06:00 [medline]PHST- 2017/11/28 06:00 [entrez]AID - S0304-3835(17)30740-1 [pii]AID - 10.1016/j.canlet.2017.11.018 [doi]PST - ppublishSO - Cancer Lett. 2018 Feb 28;415:11-19. doi: 10.1016/j.canlet.2017.11.018. Epub 2017 Nov22.</pre></div></body></html>().
PubMed ID: 29174803
DOI: S0304-3835(17)30740-1
Abstract:
Methyltransferase-like 3 (METTL3) is involved in RNA metabolism throughN6-methyladenosine (m(6)A) modification. However, whether METTL3 participates in theprogression of breast cancer is unclear. Aberrant expression of Mammalian hepatitisB X-interacting protein (HBXIP) drives the aggressiveness of breast cancer. Here, weare interested in the potential links between HBXIP and METTL3 in breast cancer. Weshowed that the expression of METTL3 was positively related to that of HBXIP inclinical breast cancer tissues. Moreover, HBXIP could up-regulate METTL3 in breastcancer cells. Mechanistically, HBXIP modulated METTL3 by inhibiting miRNA let-7g,which down-regulated the expression of METTL3 by targeting its 3'UTR. Strikingly, wefound that METTL3 promoted the expression of HBXIP through m(6)A modification.Furthermore, overexpressed HBXIP could rescue the inhibited-proliferation andenhanced-apoptosis induced by silencing of METTL3 in breast cancer cells. Thus, weconclude that HBXIP up-regulates METTL3 by suppressing let-7g, in which METTL3increased HBXIP expression forming a positive feedback loop ofHBXIP/let-7g/METTL3/HBXIP, leading to accelerated cell proliferation in breastcancer. Our finding provides new insights into the mechanism of the mutualregulation between HBXIP and METTL3 in the progression of breast cancer.CI - Copyright © 2017 Elsevier B.V. All rights reserved.