Knockdown of microRNA-203 alleviates LPS-induced injury by targeting MCL-1 in C28/I2 chondrocytes
Authors: Changfu Zhao
Tao Yu
Hui Jin
Yang Wang
Journal: Experimental cell research (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Inflammatory cytokines; LPS; MCL-1; MicroRNA−203; Osteoarthritis.
Affiliations: Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun 130033, China., Department of Orthopedics, The Second Hospital of Jilin University, Changchun 130041, China., Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun 130033, China. Electronic address: .

Abstract:  Several microRNAs (miRs) are associated with osteoarthritis (OA) and are also functionally implicated in the pathogenesis of the disease. This study was aimed to investigate the potential roles of miR-203 in the development and progression of OA, as well as to illustrate the possible molecular mechanism. OA was simulated in human cartilage C28/I2 cells with treatments of lipopolysaccharide (LPS). LPS-induced cell injury was evaluated according to cell viability, apoptosis and release of pro-inflammatory cytokines. Expression of miR-203 after LPS treatment was assessed. Then, miR-203 was aberrantly expressed, followed by evaluation of LPS-induced cell injury. The target gene of miR-203 was virtually screened by bioinformatics method and verified by luciferase assay. Moreover, the potential associated signaling pathways were also investigated. Results showed that LPS induced decrease of cell viability and increases of cell apoptosis, release of inflammatory cytokines and expression of miR-203. LPS-induced alterations were aggravated by miR-203 overexpression but were alleviated by miR-203 inhibition. Myeloid cell leukemia-1 (MCL-1) was hypothesized and subsequently verified to be a target of miR-203, and miR-203 inhibition affected C28/I2 cells through up-regulating MCL-1. In addition, LPS-induced down-regulations of key kinases as well as phosphorylated kinases were further down-regulated by miR-203 overexpression but were abrogated by miR-203 inhibition. In conclusion, this study suggests that miR-203 suppression may inhibit the progression of OA by targeting MCL-1 and activating the Wnt/β-Catenin and JAK/STAT signal pathways. 

Retracted: Yes

PubPeer comments:
 This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels. Despite these similarities, these papers are authored by researchers from different departments and institutes, with almost no overlap in authors. The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing A more detailed description of this set of papers, suspected to all be generated by a common source, a paper mill , can be found here: * https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers (January 2020) * https: scienceintegritydigest.com 2020 02 21 the-tadpole-paper-mill (February 2020) The same paper mill has been described in these papers: * Jana Christopher - Systematic fabrication of scientific images revealed - FEBS Letters (2018) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13201 * Jennifer A Byrne and Jana Christopher - Digital magic, or the dark arts of the 21st centuryu2014how can journals and peer reviewers detect manuscripts and publications from paper mills? - FEBS Letters (2020) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13747 , 
 Retracted [1 August 2022] . ------------------------ This article has been retracted at the request of the Editor-in-Chief. Given the comments of Dr Elisabeth Bik regarding this article u2026u201c the Western blot bands in all 400+ papers are all very regularly spaced and have a smooth appearance in the shape of a dumbbell or tadpole, without any of the usual smudges or stains. All bands are placed on similar looking backgrounds, suggesting they were copy pasted from other sources, or computer generatedu201d, the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article. ,