Evidence map›Paper›PMID 24648519›Full record

ArticleThe Journal of biological chemistry2014

Ras-induced epigenetic inactivation of the RRAD (Ras-related associated with diabetes) gene promotes glucose uptake in a human ovarian cancer model.

Yan Wang, Guiling Li, Fengbiao Mao, Xianfeng Li, Qi Liu, Lin Chen, Lu Lv, Xin Wang, Jinyu Wu, Wei Dai and 4 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

25 citing papers in PubMed, 37 citations in OpenAlex.

  1. The Bidirectional Relationship Between Diabetes and Cancer: Mechanistic Insights, Epigenetic Intermediaries, and Therapeutic Approaches.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 1 country.

Yan WangFrom the Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China, the University of the Chinese Academy of Sciences, Beijing 100080, China.
Guiling Lithe Institute of Genomic Medicine, Wenzhou Medical University, 268 West Xueyuan Road, Wenzhou, Zhejiang Province 325000, China.
Fengbiao Maothe University of the Chinese Academy of Sciences, Beijing 100080, China, the Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
Xianfeng Lithe State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan Province 410078, China, and.
Qi Liuthe Institute of Genomic Medicine, Wenzhou Medical University, 268 West Xueyuan Road, Wenzhou, Zhejiang Province 325000, China.
Lin Chenthe Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
Lu Lvthe Institute of Genomic Medicine, Wenzhou Medical University, 268 West Xueyuan Road, Wenzhou, Zhejiang Province 325000, China.
Xin Wangthe Institute of Genomic Medicine, Wenzhou Medical University, 268 West Xueyuan Road, Wenzhou, Zhejiang Province 325000, China.
Jinyu Wuthe Institute of Genomic Medicine, Wenzhou Medical University, 268 West Xueyuan Road, Wenzhou, Zhejiang Province 325000, China.
Wei DaiFrom the Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
Guan Wangthe Department of Obstetrics and Gynecology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
Enfeng Zhaothe Department of Obstetrics and Gynecology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
Kai-Fu Tangthe Institute of Genomic Medicine, Wenzhou Medical University, 268 West Xueyuan Road, Wenzhou, Zhejiang Province 325000, China, tangkaifu@hotmail.com.
Zhong Sheng Sunthe Institute of Genomic Medicine, Wenzhou Medical University, 268 West Xueyuan Road, Wenzhou, Zhejiang Province 325000, China, the Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China, zhongshengsun@yeah.net.
Wenzhou Medical University · CNChinese Academy of Sciences · CNPeople's Liberation Army No. 150 Hospital · CNCentral South University · CNInstitute of Psychology, Chinese Academy of Sciences · CNUniversity of Chinese Academy of Sciences · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

RRAD (Ras-related associated with diabetes) is a small Ras-related GTPase that is frequently inactivated by DNA methylation of the CpG island in its promoter region in cancer tissues. However, the role of the methylation-induced RRAD inactivation in tumorigenesis remains unclear. In this study, the Ras-regulated transcriptome and epigenome were profiled by comparing T29H (a Ras(V12)-transformed human ovarian epithelial cell line) with T29 (an immortalized but non-transformed cell line) through reduced representation bisulfite sequencing and digital gene expression. We found that Ras(V12)-mediated oncogenic transformation was accompanied by RRAD promoter hypermethylation and a concomitant loss of RRAD expression. In addition, we found that the RRAD promoter was hypermethylated, and its transcription was reduced in ovarian cancer versus normal ovarian tissues. Treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine resulted in demethylation in the RRAD promoter and restored RRAD expression in T29H cells. Additionally, treatment with farnesyltransferase inhibitor FTI277 resulted in restored RRAD expression and inhibited DNA methytransferase expression and activity in T29H cells. By employing knockdown and overexpression techniques in T29 and T29H, respectively, we found that RRAD inhibited glucose uptake and lactate production by repressing the expression of glucose transporters. Finally, RRAD overexpression in T29H cells inhibited tumor formation in nude mice, suggesting that RRAD is a tumor suppressor gene. Our results indicate that Ras(V12)-mediated oncogenic transformation induces RRAD epigenetic inactivation, which in turn promotes glucose uptake and may contribute to ovarian cancer tumorigenesis.

Indexed as

Gene SilencingAdultAgedAnimalsBiological TransportCarcinogenesisCell Line, TumorCell Transformation, NeoplasticDNA MethylationEpithelial CellsFemaleGene Expression Regulation, NeoplasticGlucoseHumansLactic AcidMiceGlucoseHRAS protein, humanLactic AcidProto-Oncogene Proteins p21(ras)ras ProteinsRRAD protein, humanDNA MethylationMetabolismOncogenic TransformationOvarian CancerRasRRADTumor Suppressor Gene

Identifiers

PMID24648519
PMCPMC4022888
OpenAlexW2024890690

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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 OpenQuestion graph.