Up-regulation of miR-146a increases the sensitivity of non-small cell lung cancer to DDP by downregulating cyclin J
Authors: Xiaoting Chen
Gang Wu
Bin Ke
Zhaozhong Xu
Weiqiang Jiang
Lin Shi
Yuanyuan Huang
Yanjing Wang
Journal: BMC Cancer (2017)
Discipline: CLINICAL MEDICINE
Keywords: CCNJ; DDP-resistance; NSCLC; miR-146a.
Affiliations: Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510282, People's Republic of China., Department of Emergency, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510282, People's Republic of China., Department of Cancer Center, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510282, People's Republic of China., Department of VIP & Traditional Chinese Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People's Republic of China., Department of Traditional Chinese Medicine, The First Affiliated Hospital of Sun Yet-sen University, 58 Second Zhongshan Road, Guangzhou, Guangdong, 510080, People's Republic of China. .

Abstract:  Background: Cisplatin (DDP)-based chemotherapy is the common first-line therapy for lung cancer. However, their efficacy is often limited by primary drug resistance and/or acquired drug resistance. The aim of this study was to investigate the function of miRNA-146a (miR-146a) in DDP-resistant non-small cell lung cancer (NSCLC), as well as the underlying mechanisms. Methods: The effect of overexpression of miR-146a and/or knockdown of cyclin J (CCNJ) in A549/DDP and SPC-A1/DDP cells were investigated as follows. The cellular sensitivity to DDP, cell apoptosis, cell cycle and cell mobility were detected by CCK-8, flow cytometry, hoechst staining and cell invasion/migration assay, respectively. The effects of miR-146a overexpression in NSCLC resistant cells were further analyzed in a nude mouse xenograft model. Results: Overexpression of miR-146a and/or knockdown of CCNJ significantly increased the sensitivity to DDP in A549/DDP and SPC-A1/DDP cells compared to NC group via arresting cell cycle, enhancing cell apoptosis, inhibiting cell viability and motility in vitro and in vivo. Furthermore, miR-146a could specially degrade the mRNA of CCNJ, as examined by dual luciferase report assay. Conclusion: The study indicates a crucial role of miR-146a in the development of acquired drug resistance to DDP in NSCLC cells. Further understanding of miR-146a mediated crosstalk networks may promote the clinical use of miR-146a analogue in NSCLC therapy. 

Retracted: No

PubPeer comments:
 Some of the flow cytometry panels in Figures 1D, 4D, and 6C appear to share unexpected similarities. Rounded boxes of the same color draw attention to areas that look similar. ![file] , 
 *[left]* Fig 5C from  Clinical Significance and Tumor-Suppressive Function of miR-516b in Nonsmall Cell Lung Cancer ([Zhu et al 2017] ). *[right]* **Figs 2A B, 5A B, 7A B**. ![] , 
 Figs 2A B, 5A B, 7A B again. ![] Panels seem to be the sources of Figs 2e, 4e, 5e from  MiRu2010191u20105p inhibits lung adenocarcinoma by repressing SATB1 to inhibit Wnt pathway ([Zhou et al 2020] ). ![file] , 
 *[above]* Fig 7C from  Regulation of human glioma cell apoptosis and invasion by miR-152-3p through targeting DNMT1 and regulating NF2 : MiR-152-3p regulate glioma cell apoptosis and invasion ([Sun et al 2017] ). *[below]* **Fig 6D**. ![file] Overlap marked. No authors in common. I have concerns. , 
 *[left]* Fig 4,  (A) Migration and invasion of SPC-A1 cells. (B) Migration and invasion of H1299 cells. From  Overexpression of NR4A1 is associated with tumor recurrence and poor survival in non-small-cell lung carcinoma ([Zhu et al 2017] ) *[right]* **Fig 7A B**. ![file] Overlap marked. Two unrelated groups of authors seem to have had access to the same pool of cell-culture images. , 
 #1 As noted by Elisabeth Bik, several pairs of flow-cytometry plots share enough points in common that they presumably came from an experimental data-set that has been filtered through different gates, Here, focusing on the right-hand panels from Fig 6C: ![file] Side-by-side, marking some areas of special similarity: ![file] Color-reversing one panel and superimposing it on the other so that points cancel out if they are present in both: ![file] , 
 #1 Dear Elisabeth M Bik I m very sorry, the corresponding information was not received in time. Regarding the issue of flow cytometry, thank you very much for your question. We are now verifying the original data, and will finally publish the verified results and data as soon as possible. Warm regardsuff0cBin Ke , 
 #2Dear Hoya camphorifolia I am the corresponding author of this paper. Thank you for your comments. We immediately checked the original data of the experiment. we confirmed that our original data not been sent to anybody. The data used in our paper that were published first. However, we do not know that why the data appeared in the followed paper. Because of the same pictures in the different paper, we are shocked. Below we showed the original data that we saved. Warm regardsuff0cBin Ke ![file] ![file] ![file] , 
 #3 Dear Hoya camphorifolia I am the corresponding author of this paper. Thank you for your comments. We immediately checked the original data of the experiment. we confirmed that our original data not been sent to anybody. The data used in our paper that were published first. However, we do not know that why the data appeared in the followed paper. Because of the same pictures in the different paper, we are shocked. Below we showed the original data that we saved. Warm regardsuff0cBin Ke ![file] ![file] ![file] , 
 #4 Dear Hoya camphorifolia I am the corresponding author of this paper. Thank you for your comments. We immediately checked the original data of the experiment. we confirmed that our original data not been sent to anybody. The data used in our paper that were published first. However, we do not know that why the data appeared in the followed paper. Because of the same pictures in the different paper, we are shocked. Below we showed the original data that we saved. Warm regardsuff0cBin Ke ![file] ![file] ![file] , 
 #5 Dear Hoya camphorifolia I am the corresponding author of this paper. Thank you for your comments. We immediately checked the original data of the experiment. we confirmed that our original data not been sent to anybody. The data used in our paper that were published first. However, we do not know that why the data appeared in the followed paper. Because of the same pictures in the different paper, we are shocked. Below we showed the original data that we saved. Warm regardsuff0cBin Ke ![file] ![file] ![file] , 
 #6 Dear Hoya camphorifolia I am the corresponding author of this paper. Regarding the issue of flow cytometry, thank you very much for your question. We are now verifying the original data, and will finally publish the verified results and data as soon as possible. Warm regardsuff0cBin Ke ,