Up-regulation of microRNA-340 promotes osteosarcoma cell apoptosis while suppressing proliferation, migration, and invasion by inactivating the CTNNB1-mediated Notch signaling pathway
Authors: Bao-Long Pan
Yan-Juan Dai
Li Pan
Yu-Xi Yang
Zong-Wu Tong
Ling Wu
Zi-Qian He
Jun-Long Liao
Ling Tan
Hu-Huan Li
You-Guang Huang
Journal: Bioscience Reports (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CTNNB1; Invasion; MicroRNA-340; Notch signaling pathway; Osteosarcoma
Affiliations: Department of Laboratory, People's Hospital of Yuxi City, Yuxi 653100, P.R. China., Department of Quality Control, Central Blood Station of Yuxi City, Yuxi 653100, P.R. China., Tumor Markers Research Center, Tumor Institute of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, P.R. China., Department of Nephrology, People's Hospital of Yuxi City, Yuxi 653100, P.R. China  ., Department of Rehabilitation Medicine, People's Hospital of Yuxi City, Yuxi 653100, P.R. China  .

Abstract:  Osteosarcoma (OS) is the most common histological form of primary bone cancer. It is most prevalent in teenagers and young adults. The present study aims at exploring the regulatory effect of microRNA-340 (miR-340) on OS cell proliferation, invasion, migration, and apoptosis via regulating the Notch signaling pathway by targeting Œ≤-catenin (cadherin-associated protein) 1 (CTNNB1). OS tissues belonging to 45 patients and normal femoral head tissues of 45 amputees were selected. Cells were allocated to different groups. In situ hybridization was performed to determine the positive rate of miR-340 expression while immunohistochemistry was used to determine that of CTNNB1 and B-cell lymphoma 2 (Bcl-2). We used a series of experiments to measure the expressions of related factors and assess rates of cell proliferation, migration, invasion, cycle, and apoptosis respectively. Our results show that miR-340 was expressed a higher level in normal tissue than OS tissue. Expression of Notch, CTNNB1, hairy and enhancer of split 1 (Hes1), Bcl-2, Runt-related transcription factor 2 (Runx2), and osteocalcin increased and that of miR-340, Bcl-2 interacting mediator of cell death (BIM), and Bcl-2 associated protein X (Bax) decreased in OS tissues. U-2OS cell line had the highest miR-340 expression. We also found that the up-regulation of miR-340 had increased expression of miR-340, BIM, and Bax but decreased expression of Notch, CTNNB1, Hes1, Bcl-2, Runx2, and osteocalcin. Up-regulation of miR-340p lead to increased cell apoptosis, suppressed cell proliferation, migration, and invasion. Our study demonstrates that overexpression of miR-340 could suppress OS cell proliferation, migration, and invasion as well as promoting OS cell apoptosis by inactivating the Notch signaling pathway via down-regulating CTNNB1. Functional miR-340 overexpression might be a future therapeutic strategy for OS. 

Retracted: Yes

PubPeer comments:
 This paper is one of a set of (at least) 6 papers that appear to show very similar photos. The photos might be showing the same materials across papers, but in all cases (with 1 exception, see below), no mentioning is made that the photo had been published before. The 6 papers, all by the same research group, are the following: * Paper 1: Derick C Miller, Anil Thapa, Karen M Haberstroh, Thomas J Webster - Enhanced functions of vascular and bladder cells on poly-lactic-co-glycolic acid polymers with nanostructured surfaces - IEEE Transactions on NanoBioscience (2002) - DOI: 10.1109 TNB.2002.806917 (this paper) * Paper 2: Sarina Kay, Anil Thapa, Karen M. Haberstroh, Thomas J. Webster - Nanostructured Polymer Nanophase Ceramic Composites Enhance Osteoblast and Chondrocyte Adhesion - Tissue Engineering 2002 - DOI: 10.1089 10763270260424114 * Paper 3: Anil Thapa, Derick C. Miller, Thomas J. Webster, Karen M. Haberstroh - Nano-structured polymers enhance bladder smooth muscle cell function - Biomaterials 24 (2003) 2915u20132926 - DOI: 10.1016 S0142-9612(03)00123-6 * Paper 4: Anil Thapa, Thomas J. Webster, Karen M. Haberstroh - Polymers with nano-dimensional surface features enhance bladder smooth muscle cell adhesion - J Biomed Mater Res 67A: 1374u20131383, 2003 - DOI: 10.1002 jbm.a.20037 * Paper 5: Derick C. Miller, Anil Thapa, Karen M. Haberstroh, Thomas J. Webster - Endothelial and vascular smooth muscle cell function on poly(lactic-co-glycolic acid) with nano-structured surface features - Biomaterials 25 (2004) 53u201361 - DOI: 10.1016 S0142-9612(03)00471-X * Paper 6: Rylie J. Vance, Derick C. Miller, Anil Thapa, Karen M. Haberstroh, Thomas J. Webster - Decreased fibroblast cell density on chemically degraded poly-lactic- co-glycolicacid, polyurethane, and polycaprolactone - Biomaterials 25 (2004) 2095u20132103 - DOI: 10.1016 j.biomaterials.2003.08.064 Could the authors please clarify if the similar photos indeed show the exact same samples across these 6 papers, and if permission for image reuse was obtained? , 
 Here, boxes of the same color highlight panels that look similar across papers. * Paper 1: Miller 2002 IEEE Figure 3  * Paper 3: Thapa 2003 Biomat Figure 6  * Paper 5: Miller 2004 Biomat Figure 3  * Paper 6: Vance 2004 Biomat Figure 1  , 
 The second group of photographic panels that look similar: * Paper 2: Kai 2002 Tissue Eng Figure 1  * Paper 3: Thapa 2003 Biomat Figure 2  * Paper 4: Thapa 2003 JBM Figure 1  , 
 The third set of similar looking images is the following. * Paper 3: Thapa 2003 Biomat Figure 3  * Paper 4: Thapa 2003 JBM Figure 2 (reused with permission from Paper 3)  * Paper 4: Thapa 2003 JBM Figure 3  * Paper 6: Vance 2004 Biomat Figures 2 and 3  ,