Inhibitory role of large intergenic noncoding RNA-ROR on tamoxifen resistance in the endocrine therapy of breast cancer by regulating the PI3K/Akt/mTOR signaling pathway
Authors: Fang Wang
Peng-Wei Lu
Yuan-Ting Gu
Lin Li
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PI3K/Akt/mTOR signaling pathway; autophagy; breast cancer; large intergenic noncoding RNA-ROR; tamoxifen.
Affiliations: Department of Breast Surgery; The First Affiliated Hospital of Zhengzhou University; Zhengzhou China

Abstract:  Breast cancer (BC) is the second-leading cause of central nervous system metastases among severe malignancies. This study aimed at investigating the underlying mechanism by which large intergenic noncoding RNA-regulator of reprogramming (lincRNA-ROR) affects the tamoxifen (TAM) resistance of BC cells by regulating the PI3K/Akt/mTOR signaling pathway. Immortalized human mammary epithelial cell line (MCF10A) and BC cell lines (MCF-7, MDA-MB-231, T47D, BCAP-37, and ZK-75-1) were cultured, and BC tissues and adjacent normal breast tissues were collected from 152 BC patients. LincRNA-ROR expression in tissues and cells were detected using reverse transcription quantitative polymerase chain reaction. RNA interference was used to silence lincRNA-ROR in MDA-MB-231 cells, and then the cell proliferation and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and annexin-V and propidium iodide (PI) double staining respectively. The expression of apoptosis-related proteins and PI3K/Akt/mTOR signaling pathway-related proteins was measured by performing western blot assay. The BC tissues and cells presented a higher expression of lincRNA-ROR. MAD-MB-231 cells exhibited the highest lincRNA-ROR expression. After lincRNA-ROR silencing, MAD-MB-231 cells showed decreased proliferation, and increased sensitivity to TAM. Besides, the apoptosis-promoting effect of TAM on MAN-MB-231 cells significantly increased. The expression of PI3K/Akt/mTOR signaling pathway-related proteins and the PI3K/Akt/mTOR signaling pathway were repressed by TAM after silencing lincRNA-ROR. Our study demonstrated that silencing lincRNA-ROR could increase the sensitivity of BC MAD-MB-231 cells to TAM by suppressing the activation of P13K/Akt/mTOR signaling pathway. 

Retracted: Yes

PubPeer comments:
 Fig 4A.  Increased effects of TAM on the apoptosis of MDAu2010MB231 cells after silencing lincRNAu2010ROR. After 48 hr of treatment with 1 u03bcM TAM: (a) the images about MDAu2010MBu2010231 cell apoptosis in each group detected by FCM . ![file] What produced the peculiar stratified appearance of dots in the upper right quadrants? Has anyone encountered a similar artifact in the past? I am also curious about the recurring strip of points cells along the bottom of each scatterplot. ![file] , 
 Fig 2(b).  Cell morphology in each group of cells after silencing lincRNAu2010ROR under a microscope (u00d7100; scale bar: 100 u03bcm). Compared with the blank group, MDAu2010MBu2010231 cell morphology significantly changed after transfection with silencing lincRNAu2010ROR, but no obvious morphological change was shown in cells in the NC group . ![file] , 
 Retracted [20 July 2021] . ---------------------------------------------- The above article, published online on 26 August 2018 in Wiley Online Library , has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found. Thus, the editors consider the conclusions of this article to be invalid. ,