Aberrant miR-1246 expression promotes radioresistance in non-small cell lung cancer: a potential prognostic biomarker and radiotherapy sensitization target
Authors: Juan Wang
Xiuping Ding
Qiang Cao
Liyuan Fan
Baosheng Li
Journal: American journal of cancer research (2020)
Discipline: CLINICAL MEDICINE
Keywords: CDR1as; YY1; autophagy; mTOR; miR-1246
Affiliations: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences Jinan 250117, China., Cheeloo College of Medicine, Shandong University Jinan 250112, China., School of Computer Science and Engineering, Southeast University Nanjing 211189, China.

Abstract:  Radiosensitivity varies among patients with non-small cell lung cancer (NSCLC). In this work, we aimed to investigate microRNAs associated with this heterogeneity among individuals. We selected miR-1246 from the microRNAs that were revealed by microarray experiments to be differentially expressed between radioresistant and parental cell lines. Both intracellular and extracellular miR-1246 was found to be upregulated after irradiation in a time-dependent pattern, resulting in increased radioresistance of NSCLC cells. We found that mTOR was a direct target gene of miR-1246, which mediated miR-1246-induced autophagy activation. Yin Yang-1 (YY1) was demonstrated to be a new transcription factor that regulates miR-1246 and CDR1as was found to be a circular RNA that sequesters miR-1246, which was confirmed in NSCLC cells and clinical samples. Finally, combining these data with the results from The Cancer Genome Atlas (TCGA), we verified that miR-1246 could be used as a biomarker to predict NSCLC patients' radiosensitivity and prognosis. Overall, our study fully investigated the effect of miR-1246 on radiosensitivity and comprehensively investigated the potential of miR-1246 as a prognostic biomarker and radiotherapy sensitization target. 

Retracted: Yes

PubPeer comments:
 Figure 4. Some panels in Figure 4C and D appear to show an overlap. Boxes of the same color highlight areas that look similar to each other. The labels and legend are not sufficiently clear to know which samples represent different experiments. Could the authors please clarify if panels with overlapping areas represent the same experiments? ![file] , 
 Figure 9. * Aqua blue boxes: The  Low and  High CDR1as panels appear to look very similar. ![file] Text in the Results referring to this figure:  To further confirm this relationship, we performed ISH (Figure 9) to measure the abundance of mature miR-1246 in FFPE human NSCLC biopsies (n=87). We also used IHC to detect the expression of mTOR and YY1, and we used FISH to detect CDR1as in the same patients (Figure 9). Analysing the relationship between the expression of these genes and clinicopathological factors showed that high miR-1246 expression had little correlation with clinicopathologic factors but was strongly related to the expression of mTOR, YY1, and CDR1as (Table 1).  Here is a detail of Figure 9, made lighter to bring out more details. Note that the right panel shows signals in green and blue, while the left panel only shows blue signal. ![file] , 
 Fig3 B The colonies formed picture seemed not match the survival curves. According to the survival curves, the SF of PC9-R-anta-nc at 8 Gy was about 0.03 and about 0.003 at 10Gy the SF of PC9-R-anta at 8 Gy was about 0.005 and about 0.001 at 10Gy ![file] but in the provided colonies formed picture, at 8Gy and 10Gy , the numer of colonies (should be less than 1% percent of 0Gy) and the trend of the change were werid. ![file] please provide further explainations. , 
 An additional concern, brought to my attention by a reader. A possible overlap between panels in Figure 4D and Supplemental Figure S3, if one of these images is in mirror image and stretched differently. Shown with pink boxes. ![file] , 
 #5 ![file] , 
 Running out of colours! ![file] , 
 The authors don t acknowledge any manipulation instead of saying  Qiang Cao, who was responsible for the bioinformatical and statistical analysis, insisted to withdraw this article [Retraction] Fan LY, Wang J, Cao Q, Ding XP, Li BS. American Journal Cancer Research. 2020;10:314-335. Cheeloo College of Medicine in Shandong University performed a self-check for previously published articles recently. We found several duplicate images in Figure 3 of this article. Then we re-checked the lab records and raw data to make sure of its reproducibility and reliability. Unfortunately, we did find some problems in the process and could not ensure its reliability. And the third authors, Qiang Cao, who was responsible for the bioinformatical and statistical analysis, insisted to withdraw this article. In this condition, we think this article is not suitable for publication. That was why we ask for the retraction of this published article. ,