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000126160 1001_ $$0P:(DE-HGF)0$$aBlume, C. J.$$b0$$eFirst author
000126160 245__ $$ap53-dependent non-coding RNA networks in chronic lymphocytic leukemia.
000126160 260__ $$aBasingstoke$$bNature Publ. Group$$c2015
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000126160 520__ $$aMutations of the tumor suppressor p53 lead to chemotherapy resistance and a dismal prognosis in chronic lymphocytic leukemia (CLL). Whereas p53 targets are used to identify patient subgroups with impaired p53 function, a comprehensive assessment of non-coding RNA targets of p53 in CLL is missing. We exploited the impaired transcriptional activity of mutant p53 to map out p53 targets in CLL by small RNA sequencing. We describe the landscape of p53-dependent microRNA/non-coding RNA induced in response to DNA damage in CLL. Besides the key p53 target miR-34a, we identify a set of p53-dependent microRNAs (miRNAs; miR-182-5p, miR-7-5p and miR-320c/d). In addition to miRNAs, the long non-coding RNAs (lncRNAs) nuclear enriched abundant transcript 1 (NEAT1) and long intergenic non-coding RNA p21 (lincRNA-p21) are induced in response to DNA damage in the presence of functional p53 but not in CLL with p53 mutation. Induction of NEAT1 and lincRNA-p21 are closely correlated to the induction of cell death after DNA damage. We used isogenic lymphoma cell line models to prove p53 dependence of NEAT1 and lincRNA-p21. The current work describes the p53-dependent miRNome and identifies lncRNAs NEAT1 and lincRNA-p21 as novel elements of the p53-dependent DNA damage response machinery in CLL and lymphoma.
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000126160 650_7 $$2NLM Chemicals$$aMicroRNAs
000126160 650_7 $$2NLM Chemicals$$aNEAT1 long non-coding RNA, human
000126160 650_7 $$2NLM Chemicals$$aRNA, Long Noncoding
000126160 650_7 $$2NLM Chemicals$$aRNA, Messenger
000126160 650_7 $$2NLM Chemicals$$aTP53 protein, human
000126160 650_7 $$2NLM Chemicals$$aTumor Suppressor Protein p53
000126160 7001_ $$0P:(DE-He78)2f34b89d62d5e5c651aa1e683844b092$$aHotz-Wagenblatt, A.$$b1$$udkfz
000126160 7001_ $$0P:(DE-He78)c9be4ab60d1090c3d315a2ca6905e9ea$$aHüllein, J.$$b2$$udkfz
000126160 7001_ $$0P:(DE-He78)b07a76205b49e86733668b7201520d19$$aSellner, L.$$b3$$udkfz
000126160 7001_ $$0P:(DE-He78)7f506158c27b5827cd9021cd3dad37c8$$aJethwa, A.$$b4$$udkfz
000126160 7001_ $$0P:(DE-HGF)0$$aStolz, T.$$b5
000126160 7001_ $$0P:(DE-He78)7cf71173d859413d8fab2ea590f3a338$$aSlabicki, M.$$b6$$udkfz
000126160 7001_ $$0P:(DE-HGF)0$$aLee, K.$$b7
000126160 7001_ $$aSharathchandra, A.$$b8
000126160 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, A.$$b9$$udkfz
000126160 7001_ $$0P:(DE-He78)6333b389d0abc96ef7f2f6e049a8f8c4$$aDietrich, S.$$b10$$udkfz
000126160 7001_ $$0P:(DE-HGF)0$$aOakes, C. C.$$b11
000126160 7001_ $$aDreger, P.$$b12
000126160 7001_ $$ate Raa, D.$$b13
000126160 7001_ $$aKater, A. P.$$b14
000126160 7001_ $$aJauch, A.$$b15
000126160 7001_ $$0P:(DE-HGF)0$$aMerkel, O.$$b16
000126160 7001_ $$aOren, M.$$b17
000126160 7001_ $$0P:(DE-He78)743a4a82daab55306a2c88b9f6bf8c2f$$aHielscher, T.$$b18$$udkfz
000126160 7001_ $$0P:(DE-He78)f3d5f16b49eb47520def635be98d5576$$aZenz, Thorsten$$b19$$eLast author$$udkfz
000126160 773__ $$0PERI:(DE-600)2008023-2$$a10.1038/leu.2015.119$$gVol. 29, no. 10, p. 2015 - 2023$$n10$$p2015 - 2023$$tLeukemia$$v29$$x1476-5551$$y2015
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