Evidence map›Paper›PMID 34496888›Full record

ArticleMolecular cancer2021

CircMYH9 drives colorectal cancer growth by regulating serine metabolism and redox homeostasis in a p53-dependent manner.

Xin Liu, Yunze Liu, Zhao Liu, Changwei Lin, Fanchao Meng, Lei Xu, Xiuzhong Zhang, Chong Zhang, Penbo Zhang, Shuai Gong and 4 more

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
5.9field-weighted citation impact, top 3% 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

87 citing papers in PubMed, 113 citations in OpenAlex.

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27 more citing papers are in PubMed but not listed here.

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 2 institutions in 1 country.

Xin Liu *Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
Yunze Liu *Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, China.
Zhao Liu *Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
Changwei Lin *Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
Fanchao MengDepartment of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
Lei XuDepartment of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
Xiuzhong ZhangDepartment of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
Chong ZhangDepartment of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
Penbo ZhangDepartment of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
Shuai GongDepartment of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
Nai WuDepartment of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
Zeqiang RenDepartment of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
Jun SongDepartment of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
Yi ZhangInstitute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, China. drcsuzhy@gmail.com.ORCID 0000-0001-9357-1205
Xuzhou Medical College · CNCentral South University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCircular RNAs (circRNAs) play important roles in cancer progression and metabolism regulation. Serine/glycine metabolism supports the growth of cancer cells by contributing to their anabolic demands and epigenome as well as by regulating their redox state. However, the role of circRNA in the regulation of serine/glycine metabolism has not been well elucidated.

methodsMicroarray analysis was used to screen differentially expressed novel circRNAs. qRT-PCR and FISH were utilized to analyzed the expression of circMYH9. CCK8, colony formation and FACS were used to analyze proliferation of colorectal cancer (CRC) cells. Xenograft experiments were used to analyze tumor growth in vivo. RNA-sequencing, immunoblot and LC-MS were used to identify the downstream metabolic pathway of circMYH9. ChIRP, Mass Spectrometry, RIP and RNA pulldown were utilized to test the interaction between circMYH9, hnRNPA2B1 and p53 pre-mRNA. ChIP-qPCR was used to analyze the binding sites of HIF-1α. Chemically-induced CRC mice were generated to evaluate the role of circMYH9 in tumorigenesis.

resultsWe identified an intron-derived circRNA, circMYH9, which was significantly upregulated in CRC tissues. A higher circMYH9 level correlated with shorter relapse-free survival and overall survival of CRC patients. CircMYH9 promoted serine/glycine metabolism, the NAD + /NADH ratio, and glutathione recycling and inhibited reactive oxygen species (ROS) in a p53-dependent manner, impacting tumour growth. Mechanistically, circMYH9 destabilized the pre-mRNA of p53 by recruiting hnRNPA2B1 in the nucleus. hnRNPA2B1 bound to N6-methyladenosine sites on the 3' untranslated region of p53 pre-mRNA and maintained its stability. Moreover, a lack of amino acids led to an elevated level of ROS, resulting in increased HIF1α, which promoted circMYH9 expression by binding to the promoter region. Furthermore, in vivo AAV9-mediated transfection of circMYH9 could drive chemically-induced carcinogenesis by suppressing p53 in mice.

conclusionsThe overexpression of circMYH9 promotes CRC proliferation though modulating serine/glycine metabolism and redox homeostasis in a p53-dependent manner, and targeting circMYH9 and its pathway may be an effective strategy for the treatment of CRC.

Indexed as

Oxidation-Reduction3' Untranslated RegionsAdultAgedAged, 80 and overAmino Acid SubstitutionAnimalsBiomarkers, TumorCell Line, TumorColorectal NeoplasmsFemaleGene Expression Regulation, NeoplasticHomeostasisHumansMaleMice3' Untranslated RegionsBiomarkers, TumorMYH9 protein, humanMyosin Heavy ChainsRNA, CircularSerineTumor Suppressor Protein p53circMYH9Colorectal cancerp53Redox homeostasisSerine/glycine metabolism

Identifiers

PMID34496888
PMCPMC8424912
OpenAlexW3198594777

What OpenQuestion holds

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LicenceCC BY
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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.