Methylation recognition protein YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) regulates the proliferation, migration and invasion of osteosarcoma by regulating m6A level of CCR4-NOT transcription complex subunit 7 (CNOT7)

被引:25
作者
Wei, Kang [1 ]
Gao, Yi [1 ]
Wang, Bin [1 ]
Qu, Yu-Xing [1 ]
机构
[1] Changzhou Tradit Chinese Med Hosp, Dept Orthopad 1, 25 Heping South Rd, Changzhou 213000, Peoples R China
关键词
Osteosarcoma; YTH N6-methyladenosine RNA binding protein 1 (YTHDF1); CCR4-NOT transcription complex subunit 7 (CNOT7); methylated modification; malignant progression; MESSENGER-RNA; GENE; IDENTIFICATION; TRANSLATION; PROGRESSION;
D O I
10.1080/21655979.2022.2037381
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
N6-methyladenosine (m6A) is one of the most significant modifications in human mRNAs. Emerging evidence indicates that m6A participates in the initiation and development of malignant tumors. Nevertheless, the biological roles and mechanism of m6A in osteosarcoma (OS) remain unclear. The purpose of this study was to investigate the role and mechanism of the methylation recognition protein-YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) in OS. The YTHDF1 expression in OS was detected by qRT-PCR and Western blot assay. M6A quantification was utilized to measure the methylation level of OS. Cell counting kit-8 (CCK8), 5-Ethynyl-2'-deoxyuridine (EdU) assay and transwell experiments were conducted to confirm the biological effects of YTHDF1 on OS cells. The bioinformatics websites and in vitro assays were conducted to analyze the downstream targets of YTHDF1 was upregulated in OS tissues at mRNA and protein level. The results showed that the expression level of YTHDF1 might be closely associated with the poor prognosis for OS patients. Inhibition of YTHDF1 could suppress the proliferation, migration and invasion of the OS cells. Moreover, we found that CCR4-NOT transcription complex subunit 7 (CNOT7) might be the potential target of YTHDF1, which was upregulated in OS tissues. YTHDF1 could recognize the m6A sites of CONT7 and promote its expression in an m6A manner. Moreover, methyltransferase-like 3 (METTL3) could promote the m6A level of CONT7. YTHDF1 was upregulated in OS and could promote cell proliferation, migration and invasion. The METTL3-CONT7-YTHDF1 regulatory axis might be the potential target for the prognosis and therapy of OS.
引用
收藏
页码:5236 / 5250
页数:15
相关论文
共 40 条
[1]   The structural basis for deadenylation by the CCR4-NOT complex [J].
Bartlam, Mark ;
Yamamoto, Tadashi .
PROTEIN & CELL, 2010, 1 (05) :443-452
[2]   Bone sarcomas: ESMO-PaedCan-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up [J].
Casali, P. G. ;
Bielack, S. ;
Abecassis, N. ;
Aro, H. T. ;
Bauer, S. ;
Biagini, R. ;
Bonvalot, S. ;
Boukovinas, I. ;
Bovee, J. V. M. G. ;
Brennan, B. ;
Brodowicz, T. ;
Martin-Broto, J. ;
Brugieres, L. ;
Buonadonna, A. ;
De Alava, E. ;
Dei Tos, A. P. ;
Del Muro, X. G. ;
Dileo, P. ;
Dhooge, C. ;
Eriksson, M. ;
Fagioli, F. ;
Fedenko, A. ;
Ferraresi, V. ;
Ferrari, A. ;
Ferrari, S. ;
Frezza, A. M. ;
Gaspar, N. ;
Gasperoni, S. ;
Gelderblom, H. ;
Gil, T. ;
Grignani, G. ;
Gronchi, A. ;
Haas, R. L. ;
Hassan, B. ;
Hecker-Nolting, S. ;
Hohenberger, P. ;
Issels, R. ;
Joensuu, H. ;
Jones, R. L. ;
Judson, I. ;
Jutte, P. ;
Kaal, S. ;
Kager, L. ;
Kasper, B. ;
Kopeckova, K. ;
Krakorova, D. A. ;
Ladenstein, R. ;
Le Cesne, A. ;
Lugowska, I. ;
Merimsky, O. .
ANNALS OF ONCOLOGY, 2018, 29 :79-95
[3]   hCAF1/CNOT7 regulates interferon signalling by targeting STAT1 [J].
Chapat, Clement ;
Kolytcheff, Chloe ;
Le Romancer, Muriel ;
Auboeuf, Didier ;
De La Grange, Pierre ;
Chettab, Kamel ;
Sentis, Stephanie ;
Corbo, Laura .
EMBO JOURNAL, 2013, 32 (05) :688-700
[4]   CircMYO10 promotes osteosarcoma progression by regulating miR-370-3p/RUVBL1 axis to enhance the transcriptional activity of β-catenin/LEF1 complex via effects on chromatin remodeling [J].
Chen, Junxin ;
Liu, Gang ;
Wu, Yizheng ;
Ma, Jianjun ;
Wu, Hongfei ;
Xie, Ziang ;
Chen, Shuai ;
Yang, Yute ;
Wang, Shengyu ;
Shen, Panyang ;
Fang, Yifan ;
Fan, Shunwu ;
Shen, Shuying ;
Fang, Xiangqian .
MOLECULAR CANCER, 2019, 18 (01)
[5]   RNA N6-methyladenosine modification in cancers: current status and perspectives [J].
Deng, Xiaolan ;
Su, Rui ;
Weng, Hengyou ;
Huang, Huilin ;
Li, Zejuan ;
Chen, Jianjun .
CELL RESEARCH, 2018, 28 (05) :507-517
[6]   IDENTIFICATION OF METHYLATED NUCLEOSIDES IN MESSENGER-RNA FROM NOVIKOFF HEPATOMA-CELLS [J].
DESROSIERS, R ;
FRIDERICI, K ;
ROTTMAN, F .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1974, 71 (10) :3971-3975
[7]   Prognostic factors for survival in patients with high-grade osteosarcoma using the Surveillance, Epidemiology, and End Results (SEER) Program database [J].
Duchman, Kyle R. ;
Gao, Yubo ;
Miller, Benjamin J. .
CANCER EPIDEMIOLOGY, 2015, 39 (04) :593-599
[8]   Analysis of the transcription regulator, CNOT7, as a candidate chromosome 8 tumor suppressor gene in colorectal cancer [J].
Flanagan, J ;
Healey, S ;
Young, J ;
Whitehall, V ;
Chenevix-Trench, G .
INTERNATIONAL JOURNAL OF CANCER, 2003, 106 (04) :505-509
[9]   Gene expression regulation mediated through reversible m6A RNA methylation [J].
Fu, Ye ;
Dominissini, Dan ;
Rechavi, Gideon ;
He, Chuan .
NATURE REVIEWS GENETICS, 2014, 15 (05) :293-306
[10]   New targets and approaches in osteosarcoma [J].
Gill, Jonathan ;
Ahluwalia, Manpreet K. ;
Geller, David ;
Gorlick, Richard .
PHARMACOLOGY & THERAPEUTICS, 2013, 137 (01) :89-99