Downregulation of long noncoding RNA Sox2ot protects PC-12 cells from hydrogen peroxide-induced injury in spinal cord injury via regulating the miR-211-myeloid cell leukemia-1 isoform2 axis
Authors: Xiaoqing Zheng
Jianxiong Zhuang
Liangze Wang
Dong Yin
Yunbing Chang
Bin Liu
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MCL-1; Sox2 overlapping transcript (Sox2ot); long noncoding RNA (lncRNA); miR-211; protein kinase B (Akt)/mammalian target of the rapamycin (mTOR)/p70 ribosomal S6 protein kinase (p70S6K) pathway
Affiliations: Department of Orthopedics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.

Abstract:  This study aimed to investigate the effects and possible mechanisms of long noncoding RNA (lncRNA) Sox2 overlapping transcript (Sox2ot) on hydrogen peroxide (H2 O2 )-induced injury in pheochromocytoma (PC-12) cells. PC-12 cells were treated with H2 O2 to cell injury. The cells were transfected with short-hairpin RNA directed against Sox2ot (sh-Sox2ot), small interfering RNA directed against myeloid cell leukemia-1 (MCL-1) isoform2 (si-MCL-1), a miR-211 mimic, a miR-211 inhibitor, and their negative controls. Under different transfected treatments, cell viability, migration, invasion, and apoptosis as well as the expressions of apoptosis- and autophagy-related proteins were investigated. Besides, the regulatory relationships between Sox2ot and miR-211, miR-211 and MCL-1, as well as between MCL-1 and the protein kinase B (Akt)/mammalian target of the rapamycin (mTOR)/p70 ribosomal S6 protein kinase (p70S6K) signaling pathway were explored. Suppression of Sox2ot inhibited H2 O2 -induced PC-12 cell injury by increasing cell viability, migration, invasion, and decreasing apoptosis and autophagy. Moreover, suppression of Sox2ot increased miR-211 expression and alleviated H2 O2 -induced injury in PC-12 cells possibly via upregulation of miR-211. Furthermore, MCL-1 isoform2 was identified as a direct target of miR-211 and could be negatively regulated by miR-211. Suppression of miR-211 aggravated H2 O2 -induced cell injury by regulation of MCL-1 isoform2. Besides, inhibition of miR-211 suppressed the activation of the Akt/mTOR/p70S6K signaling pathway in H2 O2 -treated PC-12 cells, which was reversed after knockdown of MCL-1 isoform2 at the same time. Our findings indicate that downregulation of Sox2ot may protect PC-12 cells from H2 O2 -induced injury in SCI via targeting the miR-211/MCL-1 isoform2 axis. MCL-1 isoform2 may further regulate the activation of the Akt/mTOR/p70S6K pathway to mediate H2 O2 -induced injury. The Sox2ot-miR-211-MCL-1 isoform2 axis may be a promising therapeutic strategy for SCI. 

Retracted: Yes

PubPeer comments:
 Fig 1,  B, cell migration, C, cell invasion and Fig 2,  D, Cell migration. E, Cell invasion . Collored boxes added. ![file] The hypothetical reviewers were evidently unconcerned to see visual motifs reoccurring repeatedly across these independent experiments, almost as if the mages were cobbled together in Photoshop. Of course they could not have been aware that the same visual motifs would also appear, in different combinations, in [Kong et al (2019)] , [Zhuang et al (2019)] and [Zhang et al (2019)] . ![] Figures 3D E and 5C D are more of the same, though at lower resolution; I have not bothered with a detailed exegesis. ![file] , 
 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 , 
 Retraction: u2018Downregulation of long noncoding RNA Sox2ot protects PCu201012 cells from hydrogen peroxideu2010induced injury in spinal cord injury via regulating the miRu2010211u2010myeloid cell leukemiau20101 isoform2 axisu2019, by Dong Yin, Xiaoqing Zheng, Jianxiong Zhuang, Liangze Wang, Bin Liu, Yunbing Chang, J Cell Biochem. 2018; 9675u20139684: The above article, published online on 26 August 2018 in Wiley Online Library , has been retracted by agreement between the authors, the journal s Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. The authors asked to retract this manuscript as some data and experiments are flawed and validity of the overall results could not be confirmed. , 
 See also: https: pubpeer.com publications 6C50A510CC3FC315AB00A28228677E , 
 http: med.china.com.cn content pid 291148 tid 1013 iswap 1 The paper  Down regulation of long noncoding RNA Sox2ot protects PC-12 cells from hydrogen peroxideu2013induced injury in spinal cord injury via regulating the miR-211-myeloid cell published by Yin Dong as the corresponding author and first author of Guangdong Provincial Peopleu2019s Hospital  Leukemia-1isoform2axis , after investigation, it has entrusted a third-party agency to write a proxy investment, and there are academic misconducts such as buying and selling papers, fabricating research processes, forging and falsifying research data, charts, conclusions, and test reports. The Guangdong Provincial People s Hospital shall deal with the parties as follows: 1. Conduct scientific research integrity admonishment talks with Yin Dong and its director, and order him to withdraw the manuscript immediately and return the award funds; 2. To Yin Dong: Announce and criticize the whole institute, record it in the database of serious untrustworthy behaviors in scientific research integrity, suspend the scientific research projects he presided over, freeze his scientific research funding, cancel his qualification to undertake financial support projects within 3 years, and suspend his graduate enrollment 3 In 2012, the application for promotion of professional and technical positions was suspended for 3 years. (Notification link: https: www.gdghospital.org.cn NewsMessage-20699.aspx) ,