Upregulation of microRNA-204 improves insulin resistance of polycystic ovarian syndrome via inhibition of HMGB1 and the inactivation of the TLR4/NF-κB pathway
Authors: Dabao Xu
Bin Jiang
Yujia Song
Shujuan Zhu
Min Xue
Journal: Cell Cycle (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: HMGB1; Polycystic ovarian syndrome; TLR4/NF-κB pathway; microRNA-204.
Affiliations: Department of Gynaecology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.

Abstract:  There is growing evidence of the position of microRNAs (miRs) in polycystic ovarian syndrome (PCOS), thus our objective was to discuss the impact of miR-204 on insulin resistance (IR) in PCOS by targeting highmobility group box protein 1(HMGB1)-mediated toll-like receptor 4(TLR4)/nuclear factor-kappa B (NF-κB) pathway.PCOS-IR patients and PCOS non-insulin resistance (PCOS-NIR) patients were included. The levels of serum sex hormones and related insulin were measured, the expression of miR-204, HMGB1, TLR4 and NF-κB p65 was detected, the diagnostic efficacy of miR-204 in PCOS-IR was analyzed, and the correlation between the expression of miR-204 in PCOS-IR and fasting blood glucose (FPG), fasting insulin (FINS), homeostasis model of assessment for insulin resistance index (HOMA-IR) was analyzed. Both in vitro and in vivo experiments were performed to elucidate the capabilities of miR-204 and HMGB1 in proliferation and apoptosis of PCOS-IR granulosa cells.MiR-204 was lowly expressed as well as HMGB1, TLR4 and NF-κB p65 were highly expressed in PCOS-IR patients. Follicule-stimulating hormone was downregulated, while luteinizing hormone, estrogen, progesterone, FPG, FINS and HOMA-IR were elevated in PCOS-IR. Upregulation of miR-204 and downregulation of HMGB1 could repress TLR4/NF-κB pathway activation, degraded insulin release and testosterone (T) leveland ascended ovarian coefficient, boosted cell proliferation and restrained apoptosis of granulosa cells. Overexpression of HMGB1 reverses the effect of upregulation of miR-204 on IR of PCOS.Our study presents that high expression of miR-204 or inhibition of HMGB1 can improve IR of PCOS via the inactivation of TLR4/NF-κB pathway. 

Retracted: Yes

PubPeer comments:
 Fig 4h.  Apoptosis of PCOS-IR granulosa cells after transfection in each group by flow cytometry. I have marked some of the regions that repeat within or between panels. ![image] , 
 Retracted [17 March 2022] . ------------------------- We, the Editors and Publisher of the journal *u202fCell Cycle*, have retracted the following article: Bin Jiang, Min Xue, Dabao Xu, Yujia Song, and Shujuan Zhu. Upregulation of microRNA-204 improves insulin resistance of polycystic ovarian syndrome via inhibition of HMGB1 and the inactivation of the TLR4 NF-u03baB pathway. Cell Cycle. 2020;19(6):697-710. doi: 10.1080 15384101.2020.1724601. Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide their original data. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u2018Retractedu2019. ,