Evidence map›Paper›PMID 33512745›Full record

ArticleMolecular oncology2021

LncRNA NKX2-1-AS1 promotes tumor progression and angiogenesis via upregulation of SERPINE1 expression and activation of the VEGFR-2 signaling pathway in gastric cancer.

Fei Teng, Ju-Xiang Zhang, Yi Chen, Xiao-Dong Shen, Chang Su, Yan-Jiao Guo, Pu-Hua Wang, Chen-Cheng Shi, Ming Lei, Yi-Ou Cao and 1 more

Open access · goldAbstract read
In one paragraph

Article in Molecular oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 1 pooled it
8.6field-weighted citation impact, top 1% 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

67 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.

  1. Pooled it
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  15. World journal of gastrointestinal oncology · 2025
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7 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

11 authors at 2 institutions in 1 country.

Fei TengDepartment of Gastrointestinal Surgery, Minhang Hospital, Fudan University, Shanghai, China.
Ju-Xiang ZhangShanghai Med-X Engineering Center for Medical Equipment and Technology, School of Biomedical Engineering, Shanghai Jiao Tong University, China.
Yi ChenDepartment of Gastrointestinal Surgery, Minhang Hospital, Fudan University, Shanghai, China.
Xiao-Dong ShenDepartment of Gastrointestinal Surgery, Minhang Hospital, Fudan University, Shanghai, China.
Chang SuDepartment of Gastrointestinal Surgery, Minhang Hospital, Fudan University, Shanghai, China.
Yan-Jiao GuoDepartment of Gastrointestinal Surgery, Minhang Hospital, Fudan University, Shanghai, China.
Pu-Hua WangDepartment of Gastrointestinal Surgery, Minhang Hospital, Fudan University, Shanghai, China.
Chen-Cheng ShiDepartment of Gastrointestinal Surgery, Minhang Hospital, Fudan University, Shanghai, China.
Ming LeiDepartment of Gastrointestinal Surgery, Minhang Hospital, Fudan University, Shanghai, China.
Yi-Ou CaoDepartment of Gastrointestinal Surgery, Minhang Hospital, Fudan University, Shanghai, China.
Shao-Qun LiuDepartment of Gastrointestinal Surgery, Minhang Hospital, Fudan University, Shanghai, China.ORCID 0000-0002-2016-0947
Fudan University · CNUniversity of Shanghai for Science and Technology · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Long noncoding RNAs (lncRNAs) can compete with endogenous RNAs to modulate the gene expression and contribute to oncogenesis and tumor metastasis. lncRNA NKX2-1-AS1 (NKX2-1 antisense RNA 1) plays a pivotal role in cancer progression and metastasis; however, the contribution of aberrant expression of NKX2-1-AS1 and the mechanism by which it functions as a competing endogenous RNA (ceRNA) in gastric cancer (GC) remains elusive. NKX2-1-AS1 expression was detected in paired tumor and nontumor tissues of 178 GC patients by quantitative reverse transcription PCR (qRT-PCR). Using loss-of-function and gain-of-function experiments, the biological functions of NKX2-1-AS1 were evaluated both in vitro and in vivo. Further, to assess that NKX2-1-AS1 regulates angiogenic processes, tube formation and co-culture assays were performed. RNA binding protein immunoprecipitation (RIP) assay, a dual-luciferase reporter assay, quantitative PCR, Western blot, and fluorescence in situ hybridization (FISH) assays were performed to determine the potential molecular mechanism underlying this ceRNA. The results indicated that NKX2-1-AS1 expression was upregulated in GC cell lines and tumor tissues. Overexpression of NKX2-1-AS1 was significantly associated with tumor progression and enhanced angiogenesis. Functionally, NKX2-1-AS1 overexpression promoted GC cell proliferation, metastasis, invasion, and angiogenesis, while NKX2-1-AS1 knockdown restored these effects, both in vitro and in vivo. RIP and dual-luciferase assays revealed that the microRNA miR-145-5p is a direct target of NKX2-1-AS1 and that NKX2-1-AS1 serves as a ceRNA to sponge miRNA and regulate angiogenesis in GC. Moreover, serpin family E member 1 (SERPINE1) is an explicit target for miR-145-5p; besides, the NKX2-1-AS1/miR-145-5p axis induces the translation of SERPINE1, thus activating the VEGFR-2 signaling pathway to promote tumor progression and angiogenesis. NKX2-1-AS1 overexpression is associated with enhanced tumor cell proliferation, angiogenesis, and poor prognosis in GC. Collectively, NKX2-1-AS1 functions as a ceRNA to miR-145-5p and promotes tumor progression and angiogenesis by activating the VEGFR-2 signaling pathway via SERPINE1.

Indexed as

Signal TransductionAnimalsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMiceMice, Inbred BALB CMice, NudeMicroRNAsNeovascularization, PathologicPlasminogen Activator Inhibitor 1RNA, Long NoncodingStomach NeoplasmsVascular Endothelial Growth Factor Receptor-2KDR protein, humanMicroRNAsMIRN145 microRNA, humanPlasminogen Activator Inhibitor 1RNA, Long NoncodingSERPINE1 protein, humanVascular Endothelial Growth Factor Receptor-2competing endogenous RNAgastric cancerNKX2-1 antisense RNA 1serpin family E member 1VEGFR-2 signaling pathway

Identifiers

PMID33512745
PMCPMC8024734
OpenAlexW3123152835

What OpenQuestion holds

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LicenceCC BY
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.