MiR-216b increases cisplatin sensitivity in ovarian cancer cells by targeting PARP1
Authors: X Lin
Z Niu
Y Tian
Y Liu
Journal: Cancer Gene Therapy (2017)
Discipline: CLINICAL MEDICINE
Keywords: Cisplatin resistance; MicroRNAs; miR-216b; Ovarian cancer cells; Drug resistance
Affiliations: Department of Obstetrics and Gynecology, Provincial Hospital Affiliated to Shandong University, Jinan, China., Department of Obstetrics and Gynecology, Liaocheng people's Hospital, Liaocheng, China.

Abstract:  Cisplatin resistance hinders the efficacy of chemotherapy in ovarian cancer. MicroRNAs (miRs) have been implicated in drug resistance in anti-cancer chemotherapy. We compared the expression profiles of miRs between cisplatin-resistant and cisplatin-sensitive ovarian cancer cells, and found that miR-216b was significantly downregulated in cisplatin-resistant ovarian cancer cells. To investigate its molecular mechanism, we performed cell viability and apoptosis assays in cisplatin-resistant ovarian cells, and found that miR-216b reduced cell viability and promoted apoptosis. Although 4 potential targets were obtained through bioinformatics, only the mRNA level of poly(ADP-ribose) polymerase (PARP)-1 was significantly regulated by miR-216b. Disruption of the complementary binding sequence of miR-216b on the 3'-untranslated region (3'-UTR) of the PARP1 led to the loss of miR-216b targeting. Spearman's correlation coefficient of the levels of miR-216b and PARP1 mRNA from 51 human ovarian cancer specimens also showed a significantly negative correlation between them. Importantly, the improved cisplatin sensitivity induced by miR-216b was markedly reversed by PARP1 overexpression. Tumor formation assay in nude mice further provided an evidence on the suppressive role of miR-216b in tumor growth. Taken together, this study demonstrated that a new miRNA, miR-216b, was involved in cisplatin resistance in ovarian cancer, which could be regarded as a potential sensitizer in cisplatin chemotherapy. 

Retracted: No

PubPeer comments:
 Figure 5a,b: there are some serious problems with the tumor size presented. Figure 2 and 4: the flow cytometry dot plots show negative values. Why? In addition, all the graphs have error in the x-axis. ![file] , 
 Thanks for your comments. This is the first author Yanjun Liu. I want to clarify these questions as below: 1. The scale bar in the figure legend is only a typo. The scale bar is 2 mm, not 10 mm in the figure legends; 2. Regarding the negative values in the flow cytometry dots, i assume this is misunderstanding. Please note that the base point is  0 , and 10^0=1, 10^1=10! There is no negative values at all. 3. I do not quite understand  error in the X-axis . There is no error in the X-axis. 4. I noticed that you placed  ? in the x-axis. I would like to point out that this is absolutely correct to mark the x-axis in this way! This is only to indicate the condition (days or concentrations) of the recorded numbers (in y-axis). Not the acutal numbers for the x-axis! , 
 Thank you for your reply. 1. So if the scale bar is 2 mm, V for the miR-NC tumor displayed is approx (11x8x8) 2 = 352 mm3. This is much smaller than presented in the graph. 2. I am sorry, I did a mistake here. 3 and4. Yes, there are errors in the x-axis, and it surprises me that you don t see it. The distance between two numbers indicates a unit and this unit remains uniform throughout a scale. Thus, a scale plays a crucial part in plotting graphs. Without scales, we wonu2019t be able to infer anything relevant from the graph. , 
 1. Please not that the tumor volume in miR-NC group varies from less than 100 mm3 to nearly 1000 mm3. Also, the images are only representative images from this group. How is it much smaller? 2. I can, for sure, to say that there are NO errors in the x-axis. As I replied before, the x-axis only represented experimental conditions in these figures. I understand what you mean, you can draw the graphs like you said. But it is absolutely correct to draw the graphs in our way as well. Please image if I draw this figure not using line graphs but bar graphs, will it also be problem? Also, if we only measure the tumor size for two days, let s say day 1 and day 100. In your way, it will leave a huge gap in the X-axis. Anyway, there are numerous publications to draw the figures in our way. I do not want to comment on what you insist, but I have no interest to discuss this anymore. Thanks for your attention, anyway. ,