Progesterone receptor antagonist provides palliative effects for uterine leiomyoma through a Bcl-2/Beclin1-dependent mechanism
Authors: Zhiting Wang
Quanling Feng
Shihong Cui
Lindong Zhang
Pingping Liu
Journal: Bioscience Reports (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: apoptosis; autophagy; mifepristone; progesterone receptor antagonist; progesterone receptor-M
Affiliations: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China., Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China .

Abstract:  Uterine leiomyoma is the most common benign smooth muscle tumor of uterus in women of reproductive age, with a high lifetime incidence. Nowadays, the exploration on the pharmacotherapies, such as progesterone receptor antagonist (PRA) requires more attention. Hence, the current study aimed to examine whether mifepristone, a PRA, influences the autophagy and apoptosis of uterine leiomyoma cells. Primary uterine leiomyoma cells were collected from 36 patients diagnosed with uterine leiomyoma to establish PR-M-positive (PR-M[+]) cells. The lentiviral vector overexpressing or silencing PR-M was subsequently delivered into one part of PR-M(+) cells in order to evaluate the role of PR-M in PR-M(+) cells. The results obtained revealed that cell viability was increased, while cell autophagy and apoptosis were diminished in the PR-M(+) cells treated with overexpressed PR-M, whereby the Bcl-2 level was elevated and the level of Beclin1 was reduced. An opposite trends were identified following treatment with knockdown of PR-M. Mifepristone at different concentrations (low, moderate, or high) was then applied to treat another part of the PR-M(+) cells. Mifepristone was identified to promote cell autophagy and apoptosis, decrease Bcl-2 level and increase Beclin1 level, accompanied by weakened interaction between Bcl-2 and Beclin1. Moreover, these effects of mifepristone on PR-M(+) cells were enhanced with increasing of the concentration. Taken together, the present study present evidence indicates the ability of PRA to regulate the Bcl-2/Beclin1 axis, ultimately promoting the autophagy and apoptosis of uterine leiomyoma cells, highlighting that PRA serves as a promising therapeutic target for the treatment of uterine leiomyoma. 

Retracted: No

PubPeer comments:
 I note that the Western blot images included in this paper seem to lack any background detail (even when I adjust brightness and contrast) and some appear to have sharp edges around the bands, although this is difficult to see. Below is an example from Figure 4C. Could the authors please provide an uncropped original scan for figure 4C? *** Closeup ![file] *** ![file] , 
 April 6, 2021 The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. , 
 *[above]* Fig 6C. *[below]* Fig 4C from  BCL2L10 BECN1 modulates hepatoma cells autophagy by regulating PI3K AKT signaling pathway ([He et al 2019] ). ![file] One immunofluorescence panel is recognisably the same, except with a much higher green channel here. , 
 #1 All the Western-Blot-like images in the paper have the same appearance of ink-blobs soaking into otherwise-featureless blotting paper. A representative sample: ![file] This seems especially implausible for the LC3-I LC3-II bands, where one would expect more parallelism between the two forms of the protein. It is surprising that the journal editors require such a long-drawn-out investigation just to decide whether the images are compatible with actual western blotting. Here is a medley of other manifestations of this imaginative style: ![] , 
 The hits keep coming. *[left]* Fig 2D from  Heme oxygenase-1 induction mediates chemoresistance of breast cancer cells to pharmorubicin by promoting autophagy via PI3K Akt pathway ([Pei et al 2018] ). *[right]* **Figs 2D** and **4B**. ![file] Could the authors comment on the shared source of the panels? ,