RNA-binding protein MEX3A controls G1/S transition via regulating the RB/E2F pathway in clear cell renal cell carcinoma.
RNA-binding protein MEX3A controls G1/S transition via regulating the RB/E2F pathway in clear cell renal cell carcinoma.
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RNA结合蛋白MEX3A通过调节透明细胞肾细胞癌中的RB/E2F通路来控制G1/S转变
DOI：
10.1016/j.omtn.2021.11.026
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发表时间：
2022-03-08
期刊：
影响因子：
--
通讯作者：
Yin D
中科院分区：
文献类型：
--
作者：
Qiu Y;Meng M;Cao C;Zhang J;Cheng X;Huang Y;Cao H;Li Y;Tian D;Huang Y;Peng L;Hu K;Zhang Y;Liao J;He J;Wang X;Lu D;Lin L;Bi X;Yin D
MEX3A is an RNA-binding protein that mediates mRNA decay through binding to 3′ untranslated regions. However, its role and mechanism in clear cell renal cell carcinoma remain unknown. In this study, we found that MEX3A expression was transcriptionally activated by ETS1 and upregulated in clear cell renal cell carcinoma. Silencing MEX3A markedly reduced clear cell renal cell carcinoma cell proliferation in vitro and in vivo. Inhibiting MEX3A induced G1/S cell-cycle arrest. Gene set enrichment analysis revealed that E2F targets are the central downstream pathways of MEX3A. To identify MEX3A targets, systematic screening using enhanced cross-linking and immunoprecipitation sequencing, and RNA-immunoprecipitation sequencing assays were performed. A network of 4,000 genes was identified as potential targets of MEX3A. Gene ontology analysis of upregulated genes bound by MEX3A indicated that negative regulation of the cell proliferation pathway was highly enriched. Further assays indicated that MEX3A bound to the CDKN2B 3′ untranslated region, promoting its mRNA degradation. This leads to decreased levels of CDKN2B and an uncontrolled cell cycle in clear cell renal cell carcinoma, which was confirmed by rescue experiments. Our findings revealed that MEX3A acts as a post-transcriptional regulator of abnormal cell-cycle progression in clear cell renal cell carcinoma. We described the comprehensive downstream targets of MEX3A using RIP-seq and eCLIP-seq. The data revealed that oncogene MEX3A was transcriptionally activated and mainly regulated G1/S transition in ccRCC, thus providing a novel molecular basis for clinical diagnosis and treatment.
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影响因子：
82.9
作者：
Klughammer J;Kiesel B;Roetzer T;Fortelny N;Nemc A;Nenning KH;Furtner J;Sheffield NC;Datlinger P;Peter N;Nowosielski M;Augustin M;Mischkulnig M;Ströbel T;Alpar D;Ergüner B;Senekowitsch M;Moser P;Freyschlag CF;Kerschbaumer J;Thomé C;Grams AE;Stockhammer G;Kitzwoegerer M;Oberndorfer S;Marhold F;Weis S;Trenkler J;Buchroithner J;Pichler J;Haybaeck J;Krassnig S;Mahdy Ali K;von Campe G;Payer F;Sherif C;Preiser J;Hauser T;Winkler PA;Kleindienst W;Würtz F;Brandner-Kokalj T;Stultschnig M;Schweiger S;Dieckmann K;Preusser M;Langs G;Baumann B;Knosp E;Widhalm G;Marosi C;Hainfellner JA;Woehrer A;Bock C
通讯作者：
Bock C
DOI：
10.1136/bmj.g4797
发表时间：
2014-11-10
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Jonasch E;Gao J;Rathmell WK
通讯作者：
Rathmell WK
影响因子：
16.6
作者：
Cano F;Rapiteanu R;Sebastiaan Winkler G;Lehner PJ
通讯作者：
Lehner PJ
影响因子：
10.5
作者：
Heilmann, Andreas M. F.;Dyson, Nicholas J.
通讯作者：
Dyson, Nicholas J.
影响因子：
5.2
作者：
Baietti, Maria Francesca;Zhao, Peihua;Sablina, Anna A.
通讯作者：
Sablina, Anna A.