RETRACTED ARTICLE: CDK4 and miR-15a comprise an abnormal automodulatory feedback loop stimulating the pathogenesis and inducing chemotherapy resistance in nasopharyngeal carcinoma
Authors: Qingping Jiang
Yejie Zhang
Zhen Liu
Xiaojun Luo
Qiong Xia
Chao Cheng
Xiaobing Long
Weiyi Fang
Journal: BMC Cancer (2016)
Discipline: CLINICAL MEDICINE
Keywords: CDK4; NPC; Tumor suppressor; miR-15a.
Affiliations: Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, P.R. China., Department of Pathology, Basic School of Guangzhou Medical University, Guangzhou, 510182, China., Cancer Research Institute, Southern Medical University, Guangzhou, 510515, China., Pediatric Center of Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, P.R. China., Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong, 510315, China., Cancer Research Institute, Southern Medical University, Guangzhou, 510515, China. ., Otorhinolaryngology of Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, P.R. China. ., Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, P.R. China. ., Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong, 510315, China. .

Abstract:  Background: In previous investigation, we reported that stably knocking down cyclin-dependent kinase 4(CDK4) induced expression of let-7c, which further suppressed cell cycle transition and cell growth by modulating cell cycle signaling in nasopharyngeal carcinoma (NPC). In this study, we further explored the molecular function and mechanism of CDK4 modulating miRNAs to stimulate cell cycle transition, cell growth, and Cisplatin (DDP) -resistance on in NPC. Methods: We identified changes in miRNAs by miRNA array and real-time PCR and the effect on DDP after knocking down CDK4 in NPC cells. Further, we investigated the molecular mechanisms by which CDK4 modulated miR-15a in NPC. Moreover, we also explored the role of miR-15a and the effect on DDP in NPC. Finally, we analyzed the correlation of miR-15a and CDK4 expression in NPC tissues. Results: In addition to let-7 family members, we observed that upregulated expression of miR-15a was significantly induced in CDK4-suppressed NPC cells. Further, we found that knocking down CDK4 suppressed c-Myc expression, and the latter directly suppressed the expression of miR-15a in NPC. Furthermore, miR-15a as a tumor suppressor antagonized CDK4 repressing cell cycle progression and cell growth in vitro and in vivo and induced the sensitivity of cells to DDP by regulating the c-Myc/CCND1/CDK4/E2F1 pathway in NPC. Finally, miR-15a was negatively weak correlated with the expression of CDK4 in NPC. Conclusions: Our studies demonstrate that CDK4 and miR-15a comprise an abnormal automodulatory feedback loop stimulating the pathogenesis and inducing chemotherapy resistance in NPC. 

Retracted: Yes

PubPeer comments:
 Concern about Figure 5E. The mouse shown on the left looks unexpectedly similar to the  shENO1+DDP mouse shown in Figure 7B of an older paper from the same group. Although the shadows appear a bit different, the mice shown in the 2 figures appear to have the same two blueish spots on their back, and the same tumor sizes. Yet, the excised tumors on the 2 photos are very different. Shown with blue boxes.  , 
 Figure 6A. * Red boxes: The 5-8F E2F1 and HONE1 E2F1 panel look remarkably similar  , 
 2021 retraction. https: bmccancer.biomedcentral.com articles 10.1186 s12885-021-08000-6 Retraction Note: BMC Cancer (2016) 16:238 https: doi.org 10.1186 s12885-016-2277-2 The Editor has retracted this article because of irregularities in two of the Figures. Specifically: In Fig. 5e the HONE1 mouse appears to be the same as the shENO1+DDP mouse in Fig. 7b in [1] but the excised tumours shown on the two photos appear to be different In Fig. 6a the 5-8F E2F1 and HONE1 E2F1 panels appear to be the same The Editor therefore no longer has confidence in the results and conclusions presented. Zhen Liu, Chao Cheng, Qingping Jiang and Weiyi Fang do not agree with this retraction. Xiaojun Luo, Qiong Xia, Yejie Zhang and Xiaobing Long have not responded to correspondence from the publisher about this retraction. Reference 1. Zhao M, Fang W, Wang Y, Guo S, Shu L, Wang L, Chen YY, Qiaofen F, Liu Y, Hua S, Fan Y, Liu Y, Deng X, Luo R, Mei Z, Jiang Q, Liu Z. CDK4 and miR-15a comprise an abnormal automodulatory feedback loop stimulating the pathogenesis and inducing chemotherapy resistance in nasopharyngeal carcinoma. Oncotarget. 2015;6:15610u201327. https: doi.org 10.18632 oncotarget.3639 ,