Evidence map›Paper›PMID 30477538›Full record

ArticleJournal of experimental & clinical cancer research : CR2018

MNAT1 is overexpressed in colorectal cancer and mediates p53 ubiquitin-degradation to promote colorectal cancer malignance.

Shan Zhou, Jinping Lu, Yuejin Li, Chan Chen, Yongqiang Cai, Gongjun Tan, Zhengke Peng, Zhenlin Zhang, Zigang Dong, Tiebang Kang and 1 more

RetractedOpen access · goldAbstract readRetracted Publication
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.3field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 16 citations in OpenAlex.

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  5. The Ubiquitin Gene Expression Pattern and Sensitivity toInternational journal of molecular sciences · 2020
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Shan Zhou *Department of Clinical Laboratory, Hunan Cancer Hospital &The affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China.
Jinping Lu *Department of Clinical Laboratory, Zhuhai Hospital, Jinan University, Zhuhai, 519000, Guangdong, China.
Yuejin Li *Department of Clinical Laboratory, Hunan Cancer Hospital &The affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China.
Chan ChenDepartment of Clinical Laboratory, Zhuhai Hospital, Jinan University, Zhuhai, 519000, Guangdong, China.
Yongqiang CaiDepartment of Clinical Laboratory, Zhuhai Hospital, Jinan University, Zhuhai, 519000, Guangdong, China.
Gongjun TanDepartment of Clinical Laboratory, Zhuhai Hospital, Jinan University, Zhuhai, 519000, Guangdong, China.
Zhengke PengDepartment of Clinical Laboratory, Zhuhai Hospital, Jinan University, Zhuhai, 519000, Guangdong, China.
Zhenlin ZhangDepartment of Clinical Laboratory, Zhuhai Hospital, Jinan University, Zhuhai, 519000, Guangdong, China.
Zigang DongHormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN, 55912, USA.
Tiebang KangState Key Laboratory of Oncology in South China and Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China.
Faqing TangDepartment of Clinical Laboratory, Hunan Cancer Hospital &The affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China. tangfaqing33@hotmail.com.ORCID http://orcid.org/0000-0003-0279-2956
Jinan University · CNCentral South University · CNSun Yat-sen University · CNUniversity of Minnesota · US

Funding

National Natural Science Foundation of China 81071718National Natural Science Foundation of China 81372282National Natural Science Foundation of China 81402265National Natural Science Foundation of China 81402368National Natural Science Foundation of China 81502346
6 · The paper itself

Abstract

backgroundMNAT1 (menage a trois 1, MAT1), a cyclin-dependent kinase-activating kinase (CAK) complex, high expresses in various cancers and is involved in cancer pathogenesis. However, mechanisms underlying its regulation in carcinogenesis are unclear.

methodsThe tissue microarray of colorectal cancer (CRC) was used to evaluate MNAT1 expressions in CRC tissues using immunohistochemistry, CRC cell lines were also detected MNAT1 expression using Western-blotting. MNAT1 and shMNAT1 vectors were constructed, and transfected into CRC cells. Cell growths of the transfected cells were observed using MTT and colony formation. The affects of MNAT1 on p53 expression were analyzed using Western-blotting and Real-time PCR. Immunoprecipitation assay was used to analyze the interaction p53 and MNAT1, and Western-blotting was used to test the effects of MNAT1 on p53 downstream molecules. The apoptosis of CRC cells with MNAT1 or shMNAT1 were analyzed using flow cytometry. BABL/c athymic nude mice were used to observe the effect of MNAT1 on CRC cell growth in vivo.

resultsMNAT1 was found to be overexpressed in CRC tissues and cells, and MNAT1 expressions in CRC tissue samples were associated with CRC carcinogenesis and poor patient outcomes. MNAT1-knockin increased CRC cell growth and colony formation, and MNAT1-knockdown dramatically decreased cell motility and invasion. MNAT1 physically interacted with p53, MNAT1 also increased the interaction of MDM2 with p53. Strikingly, MNAT1 mediated p53 ubiquitin-degradation. MNAT1 shortened p53 half-life, and ectopic MNAT1 expression decreased p53 protein stability. Moreover, MNAT1 induced RAD51 and reduced p21, cleaved-caspase3, cleaved-PARP and BAX expression. MNAT1 inhibited CRC cell apoptosis. shMANT1 decreased tumor growths in nude mice following p53 increase.

conclusionMNAT1 binds to p53, mediates p53 ubiquitin-degradation through MDM2, increases cell growth and decreases cell apoptosis, and finally promotes CRC malignance. MNAT1 binding to p53 and mediating p53 ubiquitin-degradation axis represents a novel molecular joint in the p53 pathway.

Indexed as

AdultAgedApoptosisCarcinogenesisCarrier ProteinsCell Cycle ProteinsCell Line, TumorColorectal NeoplasmsCyclin-Dependent Kinase-Activating KinaseFemaleHumansMiddle AgedTranscription FactorsTransfectionTumor Suppressor Protein p53UbiquitinCarrier ProteinsCell Cycle ProteinsCyclin-Dependent Kinase-Activating KinaseMNAT1 protein, humanTP53 protein, humanTranscription FactorsTumor Suppressor Protein p53UbiquitinColorectal cancerMNAT1p53TumorigenesisUbiquitin

Identifiers

PMID30477538
PMCPMC6258412
OpenAlexW2902769140

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.