WTAP-mediated m6A modification of lncRNA DIAPH1-AS1 enhances its stability to facilitate nasopharyngeal carcinoma growth and metastasis

被引：128

作者：

Li, Zhi-Xuan ^{[1
]}

Zheng, Zi-Qi ^{[1
]}

Yang, Pan-Yang ^{[1
]}

Lin, Li ^{[1
]}

Zhou, Guan-Qun ^{[1
]}

Lv, Jia-Wei ^{[1
]}

Zhang, Lu-Lu ^{[2
]}

Chen, FoPing ^{[1
]}

Li, Ying-Qin ^{[1
]}

Wu, Chen-Fei ^{[1
]}

Li, Feng ^{[1
]}

Ma, Jun ^{[1
]}

Liu, Na ^{[1
]}

Sun, Ying ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China,Canc Ctr, Guangdong Key Lab Nasopharyngeal Carcinoma Diag &, Guangzhou 510060, Peoples R China

[2] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Dept Mol Diagnost, State Key Lab Oncol South China,Canc Ctr, Guangzhou 510060, Peoples R China

来源：

CELL DEATH AND DIFFERENTIATION | 2022年 / 29卷 / 06期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

NONCODING RNAS; METHYLATION; PROGRESSION; EXPRESSION; INSIGHTS; ROLES; CELLS;

D O I：

10.1038/s41418-021-00905-w

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

As the most predominant RNA epigenetic regulation in eukaryotic cells, N-6-methyladenosine (m(6)A) plays a critical role in human tumorigenesis and cancer progression. However, the biological function and molecular mechanism of m(6)A regulation in naso-pharyngeal carcinoma (NPC) remain elusive. Here, we showed that Wilms' tumor 1-associating protein (WTAP) expression was apparently upregulated in NPC, and increased WTAP was associated with poor prognosis. WTAP upregulated in NPC was fine-tuned by KAT3A-mediated H3K27 acetylation. Functionally, WTAP was required for the growth and metastasis of NPC. Mechanistically, lncRNA DIAPH1-AS1 was identified as a bona fide m(6)A target of WTAP. WTAP-mediated m(6)A modification of DIAPH1-AS1 enhanced its stability relying on the m(6)A reader IGF2BP2-dependent pathway. Furthermore, DIAPH1-AS1 acted as a molecular adaptor that promoted MTDH-LASP1 complex formation and upregulated LASP1 expression, ultimately facilitating NPC growth and metastasis. Thus, WTAP-mediated DIAPH1-AS1 m(6)A methylation is required for NPC tumorigenesis and metastasis.

引用

页码：1137 / 1151

页数：15

共 56 条

[11] IGF2BP2 regulates DANCR by serving as an N6-methyladenosine reader [J].

Hu, Xiaoge ;

Peng, Wan-Xin ;

Zhou, Huaixiang ;

Jiang, Jiahong ;

Zhou, Xinchun ;

Huang, Dongsheng ;

Mo, Yin-Yuan ;

Yang, Liu .

CELL DEATH AND DIFFERENTIATION, 2020, 27 (06) :1782-1794

[12] m6A Modification in Coding and Non-coding RNAs: Roles and Therapeutic Implications in Cancer [J].

Huang, Huilin ;

Weng, Hengyou ;

Chen, Jianjun .

CANCER CELL, 2020, 37 (03) :270-288

[13] Recognition of RNA N6- methyladenosine by IGF2BP proteins enhances mRNA stability and translation [J].

Huang, Huilin ;

Weng, Hengyou ;

Sun, Wenju ;

Qin, Xi ;

Shi, Hailing ;

Wu, Huizhe ;

Zhao, Boxuan Simen ;

Mesquita, Ana ;

Liu, Chang ;

Yuan, Celvie L. ;

Hu, Yueh-Chiang ;

Huettelmaier, Stefan ;

Skibbe, Jennifer R. ;

Su, Rui ;

Deng, Xiaolan ;

Dong, Lei ;

Sun, Miao ;

Li, Chenying ;

Nachtergaele, Sigrid ;

Wang, Yungui ;

Hu, Chao ;

Ferchen, Kyle ;

Greis, Kenneth D. ;

Jiang, Xi ;

Wei, Minjie ;

Qu, Lianghu ;

Guan, Jun-Lin ;

He, Chuan ;

Yang, Jianhua ;

Chen, Jianjun .

NATURE CELL BIOLOGY, 2018, 20 (03) :285-+

[14] The emerging role of IncRNAs in cancer [J].

Huarte, Maite .

NATURE MEDICINE, 2015, 21 (11) :1253-1261

[15] Genome-Wide Identification of a Methylation Gene Panel as a Prognostic Biomarker in Nasopharyngeal Carcinoma [J].

Jiang, Wei ;

Liu, Na ;

Chen, Xiao-Zhong ;

Sun, Ying ;

Li, Bin ;

Ren, Xian-Yue ;

Qin, Wei-Feng ;

Jiang, Ning ;

Xu, Ya-Fei ;

Li, Ying-Qin ;

Ren, Jian ;

Cho, William C. S. ;

Yun, Jing-Ping ;

Zeng, Jing ;

Liu, Li-Zhi ;

Li, Li ;

Guo, Ying ;

Mai, Hai-Qiang ;

Zeng, Mu-Sheng ;

Kang, Tie-Bang ;

Jia, Wei-Hua ;

Shao, Jian-Yong ;

Ma, Jun .

MOLECULAR CANCER THERAPEUTICS, 2015, 14 (12) :2864-2873

[16] The RNA modification landscape in human disease [J].

Jonkhout, Nicky ;

Tran, Julia ;

Smith, Martin A. ;

Schonrock, Nicole ;

Mattick, John S. ;

Novoa, Eva Maria .

RNA, 2017, 23 (12) :1754-1769

[17] Emerging Roles of Non-Coding RNA Transcription [J].

Kaikkonen, Minna U. ;

Adelman, Karen .

TRENDS IN BIOCHEMICAL SCIENCES, 2018, 43 (09) :654-667

[18] Wilms' tumor 1-associating protein plays an aggressive role in diffuse large B-cell lymphoma and forms a complex with BCL6 via Hsp90 [J].

Kuai, Yue ;

Gong, Xin ;

Ding, Liya ;

Li, Fang ;

Lei, Lizhen ;

Gong, Yuqi ;

Liu, Qingmeng ;

Tan, Huajiao ;

Zhang, Xinxia ;

Liu, Dongyu ;

Ren, Guoping ;

Pan, Hongyang ;

Shi, Yaoyao ;

Berberich-Siebelt, Friederike ;

Ma, Zhengrong ;

Zhou, Ren .

CELL COMMUNICATION AND SIGNALING, 2018, 16

[19] The Critical Role of RNA m6A Methylation in Cancer [J].

Lan, Qing ;

Liu, Pei Y. ;

Haase, Jacob ;

Bell, Jessica L. ;

Huettelmaier, Stefan ;

Liu, Tao .

CANCER RESEARCH, 2019, 79 (07) :1285-1292

[20] WT1 associated protein promotes metastasis and chemo-resistance to gemcitabine by stabilizing Fak mRNA in pancreatic cancer [J].

Li, Bing-Qi ;

Liang, Zhi-Yong ;

Seery, Samuel ;

Liu, Qiao-Fei ;

You, Lei ;

Zhang, Tai-Ping ;

Guo, Jun-Chao ;

Zhao, Yu-Pei .

CANCER LETTERS, 2019, 451 :48-57

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