Downregulated microRNA‐135a ameliorates rheumatoid arthritis by inactivation of the phosphatidylinositol 3‐kinase/AKT signaling pathway via phosphatidylinositol 3‐kinase regulatory subunit 2
Authors: Qing-Hong Yu
Jing Wu
Dong-Bao Zhao
Yuan Qu
Jia-Xin Deng
Yu-Ping Zhang
Li-Gang Jie
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PI3K/AKT signaling pathway; PIK3R2; apoptosis; microRNA-135a; migration
Affiliations: Department of Rheumatology and Clinical Immunology, Zhujiang Hospital of Southern Medical University, Guangzhou, China., Department of Rheumatology and Immunology, Changhai Hospital, Second Military Medical University, Shanghai, China.

Abstract:  Synovial fibroblasts (SFs) of rheumatoid arthritis (RA) are phenotypically aggressive, typically progressing into arthritic cartilage degradation. Throughout our study, we made explorations into the effects of microRNA-135a (miR-135a) on the SFs involved in RA by mediating the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway via regulation of phosphatidylinositol 3-kinase regulatory subunit 2 (PIK3R2). The expression of PI3K was higher, the expression of PIK3R2 was lower, and AKT was phosphorylated in the RA synovial tissues, relative to the levels found in the normal synovial tissues. We predicted miR-135a to be a candidate miR targeting PIK3R2 using an online website, microRNA.org, which was verified with a dual-luciferase reporter gene assay. Subsequently, high miR-135a expression was observed in RA synovial tissues. To study the effect of the interaction between miR-135a and PIK3R2 in RA, the SFs isolated from RA samples were cultured and transfected with mimic, inhibitor, and small interfering RNA. The proliferation, invasion, and apoptosis of the SFs were detected after the transfection. The cells transfected with miR-135a inhibitor showed inhibited cell proliferation, migration, and invasion, while also displaying promoted cell apoptosis, G0/G1 cell ratio, and decreased S cell ratio, through upregulation of PIK3R2 and inactivation of the PI3K/AKT signaling pathway. These findings provided evidence that downregulation of miR-135a inhibits proliferation, migration, and invasion and promotes apoptosis of SFs in RA by upregulating the PIK3R2 coupled with inactivating the PI3K/AKT signaling pathway. The downregulation of miR-135a might be a potential target in the treatment of RA. 

Retracted: Yes

PubPeer comments:
 This article contains several [tortured phrases] that make some passages hard to parse: * **bolster vector machine** instead of the established _u2018support vector machineu2019_ * **cross breed model** instead of the established _u2018hybrid modelu2019_ * **discrete Fourier change** instead of the established _u2018Discrete Fourier Transformu2019_ * **fast Fourier change** instead of the established _u2018Fast Fourier Transformu2019_ * **fluffy deduction** instead of the established _u2018fuzzy logicu2019_ * **fluffy rationale** instead of the established _u2018fuzzy logicu2019_ * **hereditary calculation** instead of the established _u2018genetic algorithmu2019_ * **manufactured neural systems (ANNs)** instead of the established _u2018artificial neural networksu2019_ * **moving normal (ARIMA)** instead of the established _u2018Autoregressive integrated moving average (ARIMA)u2019_ * **self sorting out** instead of the established _u2018self organizingu2019_ * **squared mistake** instead of the established _u2018(mean) squared erroru2019_ * **vitality devouring** instead of the established _u2018energy consumingu2019_ * **wellness esteem** instead of the established _u2018fitness valueu2019_ Can the authors explain why they departed from the established phrases? ![file] --- ![file] --- ![file] How come these incorrect wordings survived proofreading by the coauthors, editors, referees, copy editors, and typesetters? Found with the [_Problematic Paper Screener_] . ,