MicroRNA-138 inhibits hypoxia-induced proliferation of endothelial progenitor cells via inhibition of HIF-1α-mediated MAPK and AKT signaling
Authors: Qingzhong Zeng
Weimin Zhou
Jixin Xiong
Wei Zhou
Journal: Experimental and Therapeutic Medicine (2017)
Discipline: CLINICAL MEDICINE
Keywords: endothelial progenitor cells; hypoxia; hypoxia-inducible factor-1α; microRNA-138; proliferation.
Affiliations: Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.

Abstract:  Endothelial progenitor cells (EPCs) participate in angiogenesis by differentiating into endothelial cells (ECs) and may be developed to treat ischemia/reperfusion injury. MicroRNAs (miRs) are a type of non-coding RNA that are 18-25 nucleotides in length and serve a role in angiogenesis. It has been demonstrated that miR-138 regulates hypoxia-induced EC dysfunction. However, to the best of our knowledge, the exact role of miR-138 in the regulation of hypoxia-induced EPCs has not previously been reported. In the present study, data collected from an MTT assay indicated that hypoxia treatment enhanced EPC proliferation, which was accompanied by an upregulation of hypoxia-inducible factor 1α (HIF-1α) expression. miR-138 overexpression inhibited hypoxia-induced EPC proliferation and induced cell cycle arrest at the G1 stage. A mechanistic investigation revealed that miR-138 negatively regulated HIF-1α protein levels but did not affect HIF-1α mRNA levels in EPCs. Moreover, results from a dual luciferase reporter assay demonstrated that HIF-1α was a direct target of miR-138 in EPCs. Furthermore, upregulation of miR-138 suppressed the hypoxia-induced upregulation of HIF-1α. Downstream factors of HIF-1α were also investigated and it was observed that the upregulation of miR-138 inhibited the hypoxia-induced upregulation of vascular endothelial growth factor, as well as the activity of mitogen-activated protein kinase and AKT signaling in EPCs. In summary, the present study suggested that miR-138 inhibits hypoxia-induced EPC proliferation, possibly by inhibiting HIF-1α-mediated signaling. 

Retracted: Yes

PubPeer comments:
 Fig 1E:  Euxanthone alleviated ox-LDL-induced cytotoxicity and apoptosis in HUVECs. ...Pre-treatment with 5 and 10 u03bcM euxanthone for 6 h rescued HUVECs from ox-LDL-induced ... apoptosis (E) a Could the authors comment on the similarity of the ox-LDL plot to the ACHN SphK1 shRNA result from Fig 6(b) of [Wang et al (2019)] ? ( Soy B promoted more profound apoptotic cell death in ccRCC cells with SphK1 knockdown ) Even the quadrant percentages are the same. ![file] , 
 Retracted [14 August 2020] . ---------------------------------------- This article has been retracted: please see Elsevier Policy on Article Withdrawal (http: www.elsevier.com locate withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief and the authors, as the panel u2018ox-LDL (100 u03bcg ml)u2019 from Fig. 1E appears similar to the panel u2018ACHN SphK1 shRNAu2019 from Fig. 6(b) of the article published by Luping Wang, Junyu Wang, Hong Zhao, Guoping Jiang, Xiaojie Feng, Wenxia Sui and Hongling Liu in the Naunyn-Schmiedeberg s Archives of Pharmacology 392 (2019) 551u2013563 https: doi.org 10.1007 s00210-018-01607-w. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process. , 
 http: www.most.gov.cn zxgz kycxjs kycxgzdt 202201 t20220127_179206.html Google Translated Date: January 27, 2022 14:44 Source: Ministry of Science and Technology u3000u300012. The paper  Cytoprotective effects of euxanthone against ox-LDL-induced endothelial cell injury is mediated via Nrf2 by Sun Yong from the School of Pharmacy, Qingdao University, and Li Shengnan from the Affiliated Cardiovascular Hospital of Qingdao University as the first author. After investigation, the paper was found to be fraudulent and improperly signed. Sun Yong was unaware of the authorship of the paper. Li Shengnan will be dealt with as follows: demerit for 1 year, cancel the application or application for science and technology projects (special projects, funds, etc.), science and technology awards, and qualifications for the title of science and technology talent for 5 years, cancel as a nominee or recommender, nominee or recommender, evaluation expert Wait for the qualification for 5 years, record it in the file of scientific research integrity and dishonesty, give the scientific research integrity admonition talk, cancel the participation in this year s first evaluation and excellent evaluation, and the annual evaluation shall not be determined as qualified or above. u3000u3000(Notification link: https: kjc.qdu.edu.cn info 1023 3178.htm) ,