p53-dependent non-coding RNA networks in chronic lymphocytic leukemia

被引：161

作者：

Blume, C. J. ^{[1
,2
]}

Hotz-Wagenblatt, A. ^{[3
]}

Huellein, J. ^{[1
,2
]}

Sellner, L. ^{[1
,2
,4
]}

Jethwa, A. ^{[1
,2
]}

Stolz, T. ^{[1
,2
]}

Slabicki, M. ^{[1
,2
]}

Lee, K. ^{[1
,2
]}

Sharathchandra, A. ^{[5
]}

Benner, A. ^{[6
]}

Dietrich, S. ^{[1
,2
,4
]}

Oakes, C. C. ^{[7
]}

Dreger, P. ^{[4
]}

te Raa, D. ^{[8
,9
]}

Kater, A. P. ^{[8
,9
]}

Jauch, A. ^{[10
]}

Merkel, O. ^{[1
,2
,11
]}

Oren, M. ^{[5
]}

Hielscher, T. ^{[6
]}

Zenz, T. ^{[1
,2
,4
]}

机构：

[1] Natl Ctr Tumor Dis NCT, Dept Translat Oncol, D-69120 Heidelberg, Germany

[2] German Canc Res Ctr, D-69120 Heidelberg, Germany

[3] DKFZ, Core Facil Genom & Prote, Bioinformat Grp, Heidelberg, Germany

[4] Univ Heidelberg Hosp, Dept Med 5, Heidelberg, Germany

[5] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel

[6] DKFZ, Div Biostat, Heidelberg, Germany

[7] DKFZ, Div Epigen & Canc Risk Factors, Heidelberg, Germany

[8] Univ Amsterdam, Acad Med Ctr, Dept Haematol, NL-1105 AZ Amsterdam, Netherlands

[9] Univ Amsterdam, Acad Med Ctr, Lab Expt Immunol, NL-1105 AZ Amsterdam, Netherlands

[10] Univ Heidelberg Hosp, Inst Human Genet, Heidelberg, Germany

[11] Med Univ Vienna, Inst Clin Pathol, Vienna, Austria

来源：

LEUKEMIA | 2015年 / 29卷 / 10期

关键词：

DIFFERENTIAL EXPRESSION ANALYSIS; DOWN-REGULATION; 17P DELETION; CLL PATIENTS; P53; MIR-34A; TP53; CANCER; SIGNATURE; TRANSCRIPTOME;

D O I：

10.1038/leu.2015.119

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Mutations of the tumor suppressor p53 lead to chemotherapy resistance and a dismal prognosis in chronic lymphocytic leukemia (CLL). Whereas p53 targets are used to identify patient subgroups with impaired p53 function, a comprehensive assessment of noncoding RNA targets of p53 in CLL is missing. We exploited the impaired transcriptional activity of mutant p53 to map out p53 targets in CLL by small RNA sequencing. We describe the landscape of p53-dependent microRNA/non-coding RNA induced in response to DNA damage in CLL. Besides the key p53 target miR-34a, we identify a set of p53-dependent microRNAs (miRNAs; miR-182-5p, miR-7-5p and miR-320c/d). In addition to miRNAs, the long non-coding RNAs (lncRNAs) nuclear enriched abundant transcript 1 (NEAT1) and long intergenic non-coding RNA p21 (lincRNA-p21) are induced in response to DNA damage in the presence of functional p53 but not in CLL with p53 mutation. Induction of NEAT1 and lincRNA-p21 are closely correlated to the induction of cell death after DNA damage. We used isogenic lymphoma cell line models to prove p53 dependence of NEAT1 and lincRNA-p21. The current work describes the p53-dependent miRNome and identifies lncRNAs NEAT1 and lincRNA-p21 as novel elements of the p53-dependent DNA damage response machinery in CLL and lymphoma.

引用

页码：2015 / 2023

页数：9

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