MicroRNA‚Ä?38 inhibits human aortic valve interstitial cell calcification by targeting Sp7
Authors: Dong Wang
Dongyang Zhang
Linna Tang
Rongwei Xu
Rongjian Xu
Wenjie Jiao
Min Zhao
Journal: Journal of Cellular and Molecular Medicine (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Sp7; calcific aortic valve disease; human aortic valve interstitial cells; miRNA-638; osteogenic differentiation.
Affiliations: Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China., Department of Vascular Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China., Department of Hospital Infection Control, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China., Center of Laboratory Medicine, Qilu Hospital of Shandong University (Qingdao), Qingdao, China.

Abstract:  Calcific aortic valve disease (CAVD) is a complex heart valve disease involving a wide range of pathological changes. Emerging evidence indicates that osteogenic differentiation of human aortic valve interstitial cells (hAVICs) plays a key role in valve calcification. In this study, we aimed to investigate the function of miR-638 in hAVICs osteogenesis. Both miRNA microarray assay and qRT-PCR results demonstrating miR-638 was obviously up-regulated in calcific aortic valves compared with non-calcific valves. We also proved that miR-638 was significantly up-regulated during hAVICs osteogenic differentiation. Overexpression of miR-638 suppressed osteogenic differentiation of hAVICs in vitro, whereas down-regulation of miR-638 enhance the process. Target prediction analysis and dual-luciferase reporter assay confirmed that Sp7 transcription factor (Sp7) was a direct target of miR-638. Furthermore, knockdown of Sp7 inhibited osteogenic differentiation of hAVICs, which is similar to the results observed in up-regulation miR-638. Our data indicated that miR-638 plays an inhibitory role in hAVICs osteogenic differentiation, which may act by targeting Sp7. MiR-638 may be a potential therapeutic target for CAVD. 

Retracted: No

PubPeer comments:
 A 2014 correction has been published for Figure 6. The text of the correction reads:  Panels D and F of Figure 6 were duplicated.  However, several other issues with this paper remain. For a complete inventory, here are the two duplications highlighted in the original Figure 6. Both issues in this figure have been addressed with the correction.  , 
 Not yet addressed in the correction are some unexpected similarities between panels in Figure 1F. They are highlighted here in red, yellow, and pink. Could the authors please check what happened here?  , 
 Figure 4. The GAPDH blots in B, C, and D all appear to show similarities that might be explained by a possible overlap, although maybe the authors could have a better explanation. Highlighted in dark orange and purple. Could the authors please check?  , 
 #2 Fig 1D also.  , 
 Fig 2E. Curious anomaly in the SV lane for BAX. Enhanced here by decreasing the contrast.  , 
 2020 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0228688 In a previous correction to this article [1, 2], an updated version of Fig 6 was provided to address image duplications involving the Control uPar data in Figs 6C and 6D, and the BAX blots shown in Figs 6E and 6F. In the updated figure, the panels of concern in Figs 6D and 6F were replaced with different data. Additional concerns have since been noted for other figures [1]: In Fig 1D, similarities were noted between the Con and SV plots for 5310 cells. In Fig 1F, similarities were noted between the following panels: U251 TUNEL for pU and pC; U251 DAPI for pU and pC; 5310 DAPI for pU and pC. In the U251 BAX blot in Fig 2E, when levels are adjusted it appears as though the background in the SV lane differs from the background in other lanes. GAPDH data appear similar in Fig 4B, lanes 1u20133, versus Fig 4C; and in Fig 4B, lanes 3u20135 versus Fig 4D. These figure panels represent different experimental results. In Fig 4E, when levels are adjusted there appears to be a vertical discontinuity in the p-PI3K panel before the lane 2 band. It is difficult to confirm the integrity of blot and gel images reported in the articleu2019s figures in light of the poor image quality, and the uniform appearance of the background in these panels raises concerns. The University of Illinois at Chicago investigated this work and found evidence of data falsification involving Figs 6Cu20136F. In light of the above concerns that call into question the validity and reliability of the reported results and following the outcome of the institutionu2019s investigation, the PLOS ONE Editors retract this article. The authors either did not reply to the retraction notification or could not be reached. References 1.Malla R, Gopinath S, Alapati K, Gondi CS, Gujrati M, Dinh DH, et al. (2010) Downregulation of uPAR and Cathepsin B Induces Apoptosis via Regulation of Bcl-2 and Bax and Inhibition of the PI3K Akt Pathway in Gliomas. PLoS ONE 5(10): e13731. https: doi.org 10.1371 journal.pone.0013731 pmid:21060833 2.Malla R, Gopinath S, Alapati K, Gondi CS, Gujrati M, Dinh DH, et al. (2014) Correction: Downregulation of uPAR and Cathepsin B Induces Apoptosis via Regulation of Bcl-2 and Bax and Inhibition of the PI3K Akt Pathway in Gliomas. PLoS ONE 9(1): ,