Evidence map›Paper›PMID 36474242›Full record

ArticleCancer & metabolism2022

Tadalafil increases the antitumor activity of 5-FU through inhibiting PRMT5-mediated glycolysis and cell proliferation in colorectal cancer.

Yao Shen, Pan Zhao, Kewei Dong, Jiajia Wang, Huichen Li, Mengyang Li, Ruikai Li, Suning Chen, Yuxia Shen, Zhiyu Liu and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cancer & metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

6 citing papers in PubMed, 12 citations in OpenAlex.

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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

13 authors at 4 institutions in 1 country.

Yao Shen *The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, 710032, China.
Pan Zhao *The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, 710032, China.
Kewei Dong *The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, 710032, China.
Jiajia WangThe State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, 710032, China.
Huichen LiThe State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, 710032, China.
Mengyang LiThe Faculty of Hepatopancreatobiliary Surgery, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.
Ruikai LiDepartment of Gastrointestinal Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Suning ChenDepartment of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Yuxia ShenThe State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, 710032, China.
Zhiyu LiuThe State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Mianjiao XieDepartment of Experimental Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Peng ShenDepartment of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. shenbo20110311@163.com.
Jian ZhangThe State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, 710032, China. biozhangj@fmmu.edu.cn.
Air Force Medical University · CNXijing Hospital · CNChinese People's Liberation Army · CNNanfang Hospital · CN

Funding

China Postdoctoral Science Foundation 2021M93959National Natural Science Foundation of China 82073202National Natural Science Foundation of China 82103402Research and development projects in Shaanxi Province 2022SF-603State Key Laboratory of Cancer Biology Project CBSKL2019KF02State Key Laboratory of Cancer Biology Project CBSKL2019ZZ11
6 · The paper itself

Abstract

backgroundProtein arginine methyltransferase 5 (PRMT5) is upregulated in multiple tumors and plays a pivotal role in cancer cell proliferation. However, the role of PRMT5 in colorectal cancer remains poorly understood.

methodsWe detected the expression level of PRMT5 and glycolytic enzymes using online databases and colorectal cancer cell lines by immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting. And MTT and colony formation assays were conducted to investigate cell proliferation. Then, we evaluated ECAR and OCR levels using a biological energy analyzer to investigate the energy status of colorectal cancer, and the transcriptional regulation was detected by dual luciferase reporter assay and ChIP assay. Finally, the efficacy of combined treatment of tadalafil and 5-FU was verified.

resultsPRMT5 was highly expressed in colorectal cancer tissues compared with their normal counterparts and correlated with poor prognosis in CRC patients. Then, we demonstrated that PRMT5 knockdown or loss of function attenuated the viability of CRC cells, while overexpression of PRMT5 promoted cell proliferation. Mechanistically, PRMT5 enhanced glycolysis through transcriptionally activating LDHA expression. In addition, the PRMT5 inhibitor, tadalafil, rendered CRC cells sensitive to antitumor agent 5-FU in vitro and in vivo.

conclusionsOur data indicates that PRMT5 promoted colorectal cancer proliferation partially through activating glycolysis and may be a potential target for colorectal cancer therapy.

Indexed as

5-FUColorectal cancerPRMT5Tadalafil

Identifiers

PMID36474242
PMCPMC9727889
OpenAlexW4310954204

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.