ALKBH5-mediated N6-methyladenosine modification of TRERNA1 promotes DLBCL proliferation via p21 downregulation

被引：32

作者：

Song, Wei ^{[1
,2
]}

Fei, Fei ^{[1
]}

Qiao, Fengchang ^{[3
]}

Weng, Zuyi ^{[1
]}

Yang, Yuanxun ^{[1
]}

Cao, Bei ^{[1
]}

Yue, Jing ^{[4
]}

Xu, Jiaxuan ^{[1
]}

Zheng, Meihong ^{[1
]}

Li, Juan ^{[1
]}

机构：

[1] Nanjing Univ, Med Sch, Affiliated Hosp, Phase 1 Clin Trials Unit,Nanjing Drum Tower Hosp, Nanjing 210008, Peoples R China

[2] Bengbu Med Coll, Anhui Prov Key Lab Translat Canc Res, Bengbu 233030, Peoples R China

[3] Nanjing Med Univ, Nanjing Matern & Child Hlth Care Hosp, Womens Hosp, Nanjing 210001, Peoples R China

[4] Nanjing Univ, Med Sch, Affiliated Hosp, Dept Gynaecol & Obstet,Nanjing Drum Tower Hosp, Nanjing 210008, Peoples R China

来源：

CELL DEATH DISCOVERY | 2022年 / 8卷 / 01期

基金：

中国国家自然科学基金;

关键词：

LONG NONCODING RNAS; CELL; DEMETHYLASE; METASTASIS; EXPRESSION; ENHANCER; ALKBH5;

D O I：

10.1038/s41420-022-00819-7

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Long noncoding RNAs (lncRNAs) have crucial functions in the tumorigenesis and metastasis of cancers. N-6-methyladenosine (m(6)A) modification of RNA is an important epigenetic regulatory mechanism in various malignancies. Nevertheless, the mechanism of m(6)A-modified lncRNA in diffuse large B cell lymphoma (DLBCL) has remained poorly defined. In the present study, we showed that lncRNA TRERNA1 was associated with the poor prognosis of DLBCL patients. TRERNA1 with internal m(6)A modification was highly correlated with the demethylase ALKBH5 expression. We further demonstrated that TRERNA1 was a potential downstream target of ALKBH5-mediated m(6)A modification by m(6)A-RNA sequencing and m(6)A-RIP assays. Decreased m(6)A methylation of TRERNA1 regulated by ALKBH5 was shown to regulate cell proliferation in vitro and in vivo. The results of mechanism analyses revealed that TRERNA1 recruited EZH2 to epigenetically silence the expression of the cyclin-dependent kinases inhibitor p21 by H3K27me3 modification of its promoter region. In addition, ALKBH5 further inhibited p21 expression. Taken together, our results elucidate the functional roles and epigenetic alterations of TRERNA1 through m(6)A modification in DLBCL. TRERNA1, the expression of which is upregulated by ALKBH5, acts as a scaffold that decreases p21 expression. The results of the present study provide novel targets for the diagnosis and treatment of DLBCL.

引用

页数：12

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