microRNA-335 inhibits proliferation, cell-cycle progression, colony formation, and invasion via targeting PAX6 in breast cancer cells
Authors: Yuanbiao Meng
Yubin Huang
Tianqi Liu
Xiaoyong Cai
Quanqing Zou
Jinfei Pan
Journal: Molecular Medicine Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: miRNAs; tumorigenesis; breast cancer; miR-335; PAX6
Affiliations: Department of General Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China., Department of Hepatobiliary and Endocrine Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China.

Abstract:  microRNAs (miRNAs) have been demonstrated to play crucial roles in tumorigenesis. However, the molecular mechanism underlying the roles of miRNAs in breast cancer remains largely unknown. In this study, we showed that miR-335 is downregulated in a number of breast cancer tissues and cell lines. Luciferase reporter assays identified the paired box 6 gene (PAX6) as a novel target of miR-335. Further investigation revealed that miR-335 negatively regulates the expression of PAX6 in human breast cancer MCF-7 cells. Our results further suggested that overexpression of miR-335 inhibits MCF-7 cell proliferation by inducing cell-cycle arrest at the G1 phase via targeting PAX6. Western blot analysis showed that overexpression of miR-335 promotes p27 protein expression but inhibits cyclin D1 expression in MCF-7 cells; however, overexpression of PAX6 decreased the p27 protein level but increased the cyclin D1 protein level in MCF-7 cells. Furthermore, miR-335 overexpression reduced colony formation and cellular invasion in MCF-7 cells, an effect that was reversed by PAX6 overexpression. In conclusion, this study provides novel insights into the in vitro regulatory patterns of miRNA-335 and PAX6 in breast cancer, and indicates that miRNA-335 may constitute a promising candidate for the treatment of breast cancer. 

Retracted: Yes

PubPeer comments:
 *[right]* Fig 4B.  Western blot analysis was used to determine the protein expression of p27 and cyclin D1 in MCF-7 cells following transfection with the miR-335 mimic or the PAX6 plasmid . *[left]* Fig 2B from [Luo, Li Zhang (2015)] .  Protein levels of Pax6 were determined using western blotting in A549 NSCLC cells transfected with miR-7 mimics or inhibitor, respectively. Unexpected similarity.  , 
 Fig 4A.  A cell-cycle assay was used to examine the cell-cycle distribution of MCF-7 cells following transfection with the microRNA-335 (miR-335) mimic or inhibitor, or co-transfection with the miR-335 inhibitor and the paired box 6 (PAX6) small interfering RNA (siRNA). Control, non-transfected MCF-7 cells.  Fig 4A from [Li et al (2014)] .  miR-22 inhibited E2-induced cell cycle progression in RL95-2 and Ishikawa cells. (A) Cell cycle assay was performed to investigate the effect of miR-22 on E2-induced cell cycle progression in RL95-2 and Ishikawa cells.  How to explain the shared panel? , 
 Retracted [9 July 2021] . ------------------------------------ Following the publication of this paper, it was drawn to the Editors attention by a concerned reader that the cell cycle assay data shown in Fig. 4A, and the western blotting assay data shown in Fig. 4B, were strikingly similar to data appearing in different form in other articles by different authors; furthermore, there were other possible anomalies associated with these data. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to *Molecular Medicine Reports*, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. ,