Evidence map›Paper›PMID 35953862›Full record

ArticleCancer cell international2022

Nectin-4 promotes osteosarcoma progression and metastasis through activating PI3K/AKT/NF-κB signaling by down-regulation of miR-520c-3p.

Yongheng Liu, Guanghao Li, Yan Zhang, Lili Li, Yanting Zhang, Xiaoyu Huang, Xianfu Wei, Peng Zhou, Ming Liu, Gang Zhao and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cancer cell international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

12 citing papers in PubMed, 20 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

12 authors at 1 institution in 1 country.

Yongheng Liu *Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhu Xi Road, Tiyuan Bei, Hexi District, Tianjin, 300060, People's Republic of China.
Guanghao Li *Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhu Xi Road, Tiyuan Bei, Hexi District, Tianjin, 300060, People's Republic of China.
Yan ZhangDepartment of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhu Xi Road, Tiyuan Bei, Hexi District, Tianjin, 300060, People's Republic of China.
Lili LiDepartment of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhu Xi Road, Tiyuan Bei, Hexi District, Tianjin, 300060, People's Republic of China.
Yanting ZhangDepartment of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhu Xi Road, Tiyuan Bei, Hexi District, Tianjin, 300060, People's Republic of China.
Xiaoyu HuangDepartment of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhu Xi Road, Tiyuan Bei, Hexi District, Tianjin, 300060, People's Republic of China.
Xianfu WeiDepartment of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhu Xi Road, Tiyuan Bei, Hexi District, Tianjin, 300060, People's Republic of China.
Peng ZhouDepartment of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhu Xi Road, Tiyuan Bei, Hexi District, Tianjin, 300060, People's Republic of China.
Ming LiuKey Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Gang ZhaoKey Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Jinyan FengDepartment of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhu Xi Road, Tiyuan Bei, Hexi District, Tianjin, 300060, People's Republic of China. jinyan_feng@126.com.
Guowen WangDepartment of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhu Xi Road, Tiyuan Bei, Hexi District, Tianjin, 300060, People's Republic of China. wangguowen@tmu.edu.cn.
Tianjin Medical University Cancer Institute and Hospital · CN

Funding

National Natural Science Foundation of China 81773031National Natural Science Foundation of China 81872184
6 · The paper itself

Abstract

purposeNectin-4 is specifically up-regulated in various tumors, exert crucial effects on tumor occurrence and development. Nevertheless, the role and molecular mechanism of Nectin-4 in osteosarcoma (OS) are rarely studied.

methodsThe expression of Nectin-4 and its relationship with clinical characteristics of OS were investigated using OS clinical tissues, tissue microarrays, TCGA, and GEO databases. Moreover, the effect of Nectin-4 on cell growth and mobility was detected by CCK-8, colony formation, transwell, and wound-healing assays. The RT-qPCR, Western blotting, and luciferase reporter assays were performed to explore molecular mechanisms through which Nectin-4 mediates the expression of miR-520c-3p, thus modulating PI3K/AKT/NF-κB signaling. In vivo mice models constructed by subcutaneous transplantation and tail vein injection were used to validate the functional roles of Nectin-4 and miR-520c-3p.

resultsNectin-4 displayed a higher expression in OS tumor tissues compared with normal tissues, and its overexpression was positively associated with tumor stage and metastasis in OS patients. Functionally, Nectin-4 enhanced OS cells growth and mobility in vitro. Mechanistically, Nectin-4 down-regulated the levels of miR-520c-3p that directly targeted AKT-1 and P65, thus leading to the stimulation of PI3K/AKT/NF-κB signaling. In addition, the expression of miR-520c-3p was apparently lower in OS tissues than in normal tissues, and its low expression was significantly related to tumor metastasis. Furthermore, ectopic expression of miR-520c-3p markedly blocked the effect of Nectin-4 on OS cell growth and mobility. Knockdown of Nectin-4 could suppress the tumorigenesis and metastasis in vivo, which could be remarkably reversed by miR-520c-3p silencing.

conclusionsNectin-4 as an oncogene can promote OS progression and metastasis by activating PI3K/AKT/NF-κB signaling via down-regulation of miR-520c-3p, which could represent a novel avenue for identifying a potential therapeutic target for improving patient outcomes.

Indexed as

MetastasismiR-520c-3pNectin-4OsteosarcomaPI3K/AKT/NF-κB

Identifiers

PMID35953862
PMCPMC9367085
OpenAlexW4291021460

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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.