Evidence map›Paper›PMID 33435987›Full record

ArticleJournal of orthopaedic surgery and research2021

Circular RNA circ_0081001 knockdown enhances methotrexate sensitivity in osteosarcoma cells by regulating miR-494-3p/TGM2 axis.

Wei Wei, Liefeng Ji, Wanli Duan, Jiang Zhu

Open access · goldAbstract read
In one paragraph

Article in Journal of orthopaedic surgery and research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

  1. Pooled it
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  6. Osteosarcoma in a ceRNET perspective.Journal of biomedical science · 2024
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  10. Role of microRNA-494 in tumor progression.American journal of translational research · 2023
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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

4 authors at 1 institution in 1 country.

Wei WeiDepartment of Orthopedics, Shaoxing Shangyu People's Hospital, No. 517 Civic Avenue, Baiguan Street, Shangyu District, Shaoxing, Zhejiang, 312300, China. parjpy@163.com.
Liefeng JiDepartment of Orthopedics, Shaoxing Shangyu People's Hospital, No. 517 Civic Avenue, Baiguan Street, Shangyu District, Shaoxing, Zhejiang, 312300, China.
Wanli DuanDepartment of Orthopedics, Shaoxing Shangyu People's Hospital, No. 517 Civic Avenue, Baiguan Street, Shangyu District, Shaoxing, Zhejiang, 312300, China.
Jiang ZhuDepartment of Orthopedics, Shaoxing Shangyu People's Hospital, No. 517 Civic Avenue, Baiguan Street, Shangyu District, Shaoxing, Zhejiang, 312300, China.
Shaoxing People's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCircular RNAs (circRNAs) have been shown to participate in the chemoresistance and tumorigenesis of multiple cancers. The purpose of this research was to investigate the function of circ_0081001 in methotrexate (MTX) resistance of osteosarcoma (OS) and its potential molecular mechanism.

methodsThe expression of circ_0081001, cytochrome P450 family 51 subfamily A member 1 (CYP51A1), and miR-494-3p was detected by qRT-PCR. Cell viability, apoptosis, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and transwell assay, respectively. Western blot (WB) assay was used to measure the protein levels of cleaved-caspase3 (cleaved-casp3), E-cadherin, N-cadherin, and transglutaminase-2 (TGM2). The interaction between miR-494-3p and circ_0081001 or TGM2 was predicted by bioinformatics analysis and verified using the dual-luciferase reporter assay. The mice xenograft model was established to investigate the roles of circ_0081001 in MTX resistance of OS in vivo.

resultsCirc_0081001 and TGM2 were upregulated, and miR-494-3p was downregulated in MTX-resistant OS tissues and cells. Moreover, circ_0081001 interference enhanced cell sensitivity to MTX through promoting apoptosis and inhibiting cell viability and metastasis in vitro. Furthermore, circ_0081001 was identified as a molecular sponge of miR-494-3p to upregulate TGM2 level. In addition, circ_0081001 knockdown inhibited MTX resistance via upregulating miR-494-3p and downregulating TGM2. Besides, circ_0081001 downregulation improved MTX sensitivity of OS in vivo.

conclusionKnockdown of circ_0081001 enhanced MTX sensitivity of OS cells through downregulating TGM2 by sponging miR-494-3p, elucidating a novel regulatory mechanism for chemoresistance of OS and providing a potential circRNA-targeted therapy for OS.

Indexed as

Gene Knockdown TechniquesCell Line, TumorDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticGTP-Binding ProteinsHumansMethotrexateMicroRNAsMolecular Targeted TherapyOsteosarcomaProtein Glutamine gamma Glutamyltransferase 2RNA, CircularTransglutaminasesGTP-Binding ProteinsMethotrexateMicroRNAsMIRN494 microRNA, humanProtein Glutamine gamma Glutamyltransferase 2RNA, CircularTGM2 protein, humanTransglutaminasescirc_0081001miR-494-3pMTX sensitivityTGM2

Identifiers

PMID33435987
PMCPMC7805151
OpenAlexW3120604986

What OpenQuestion holds

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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 OpenQuestion graph.