Evidence map›Paper›PMID 28821833›Full record

ArticleScientific reports2017

MicroRNA-449c-5p inhibits osteogenic differentiation of human VICs through Smad4-mediated pathway.

Rongjian Xu, Min Zhao, Yun Yang, Zhuo Huang, Chunying Shi, Xianglin Hou, Yannan Zhao, Bing Chen, Zhifeng Xiao, Jianzhou Liu and 2 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.9field-weighted citation impact, top 5% 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, 41 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. The role of microRNAs in calcific aortic valve disease.Frontiers in cardiovascular medicine · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. SMAD4 contributes to chondrocyte and osteocyte development.Journal of cellular and molecular medicine · 2022
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
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  19. Article
  20. Review
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 8 institutions in 1 country.

Rongjian XuDepartment of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
Min ZhaoCenter of Laboratory Medicine, Qilu Hospital of Shandong University (Qingdao), Qingdao, 266035, China.
Yun YangState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Zhuo HuangDepartment of Cardiac Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Chunying ShiInstitute for Translational Medicine, College of Medicine, Qingdao University, Qingdao, China.
Xianglin HouState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Yannan ZhaoState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Bing ChenState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Zhifeng XiaoState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Jianzhou LiuDepartment of Cardiac Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Qi MiaoDepartment of Cardiac Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. miaoqipumc@hotmail.com.
Jianwu DaiState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. jwdai@genetics.ac.cn.
Army Medical University · CNChinese Academy of Medical Sciences & Peking Union Medical College · CNChinese Academy of Sciences · CNInstitute of Genetics and Developmental Biology · CNAffiliated Hospital of Qingdao University · CNPeking Union Medical College Hospital · CNQilu Hospital of Shandong University · CNQingdao University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Calcific aortic valve disease (CAVD) is the most common heart valve disorder, yet its mechanism remains poorly understood. Valve interstitial cells (VICs) are the prevalent cells in aortic valve and their osteogenic differentiation may be responsible for calcific nodule formation in CAVD pathogenesis. Emerging evidence shows microRNA (miRNA, or miR) can function as important regulators of many pathological processes, including osteogenic differentiation. Here, we aimed to explore the function of miR-449c-5p in CAVD pathogenesis. In this study, we demonstrated the role of miR-449c-5p in VICs osteogenesis. MiRNA microarray assay and qRT-PCR results revealed miR-449c-5p was significantly down-regulated in calcified aortic valves compared with non-calcified valves. MiR-449c-5p overexpression inhibited VICs osteogenic differentiation in vitro, whereas down-regulation of miR-449c-5p enhanced the process. Target prediction analysis and dual-luciferase reporter assay confirmed Smad4 was a direct target of miR-449c-5p. Furthermore, knockdown of Smad4 inhibited VICs osteogenic differentiation, similar to the effect observed in up-regulation miR-449c-5p. In addition, animal experiments proved indirectly miR-449c-5p could alleviate aortic valve calcification. Our data suggested miR-449c-5p could function as a new inhibitory regulator of VICs osteogenic differentiation, which may act by targeting Smad4. MiR-449c-5p may be a potential therapeutic target for CAVD.

Indexed as

Signal Transduction3' Untranslated RegionsAnimalsAortic ValveAortic Valve StenosisBiomarkersCalcinosisCell DifferentiationCells, CulturedConnective Tissue CellsFemaleGene Expression ProfilingGene Expression RegulationGene Knockdown TechniquesHeart ValvesHumans3' Untranslated RegionsBiomarkersMicroRNAsMIRN449 microRNA, humanSmad4 ProteinSMAD4 protein, human

Identifiers

PMID28821833
PMCPMC5562804
OpenAlexW2749135737

What OpenQuestion holds

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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.