circKDM4C suppresses tumor progression and attenuates doxorubicin resistance by regulating miR-548p/PBLD axis in breast cancer
Authors: Ning Zhang
Qifeng Yang
Renbo Guo
Xiaoyan Li
Yiran Liang
Peng Su
Tingting Ma
Wenjing Zhao
Bing Chen
Yuting Sang
Dianwen Han
Yi Duan
Xiaojin Song
Lijuan Wang
Ying Liu
Hanwen Zhang
Yaming Li
Journal: Oncogene (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: circRNAs; circKDM4C; breast cancer; metastasis; prognosis
Affiliations: Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR China., Department of Pathology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR China., Department of Urology, Shandong cancer hospital affiliated to Shandong University, Jinan, Shandong, 250117, PR China., Pathology Tissue Bank, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR China., Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR China. ., Pathology Tissue Bank, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR China. .

Abstract:  Increasing evidence has indicated that circular RNAs (circRNAs) play a critical role in cancer development. However, only a small number of circRNAs have been experimentally validated and functionally annotated. In this study, using a high-throughput microarray assay, we identified a novel circRNA, circKDM4C, which was downregulated in breast cancer tissues with metastasis. Furthermore, we analyzed a cohort of breast cancer patients and found that circKDM4C expression was decreased in breast cancer tissues, and lower circKDM4C expression was associated with poor prognosis and metastasis in breast cancer. Functionally, we demonstrated that circKDM4C significantly repressed breast cancer proliferation, metastasis, and doxorubicin resistance in vitro and in vivo. Mechanistically, using a dual-luciferase activity assay and AGO2 RNA immunoprecipitation, circKDM4C was identified as a miR-548p sponge. We also found that PBLD was a direct target of miR-548p, which functioned as a tumor suppressor in breast cancer. Moreover, miR-548p overexpression was able to reverse the circKDM4C-induced attenuation of malignant phenotypes and elevated expression of PBLD in breast cancer cells. Taken together, our data indicate that circKDM4C might have considerable potential as a prognostic biomarker in breast cancer, and support the notion that therapeutic targeting of circKDM4C/miR-548p/PBLD axis may be a promising treatment approach for breast cancer patients. 

Retracted: No

PubPeer comments:
 Figure 6L. * Blue boxes: Two panels appear to show an overlap.  , 
 #1 Dear Dr. Bik, Thank you very much for your kind comment! I have immediately asked the first author and other team members to check the original data. We confirmed that the first author made mistake for the figure 6L preparation. I am sorry that I have not notified it, and we have contacted the journal office and request for a correction following normal academic procedures. Again, thank you very much for your kind efforts for the medical science. Sincerely yours Qifeng , 
 Correction, March 2021: https: www.nature.com articles s41388-021-01750-4  Unfortunately, an error occurred in Figs. 6l and S2d. The corrected figures are given below. I thank the authors and journal for addressing this issue. ,