Long non-coding RNA UCA1 promotes malignant phenotypes of renal cancer cells by modulating the miR-182-5p/DLL4 axis as a ceRNA
Authors: Lei Song
Panfeng Shang
Zhongjin Yue
Wentao Hu
Ya Wang
Yong An
Wei Wang
Journal: Molecular Cancer (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: DLL4; Renal cancer; UCA1; ceRNA; miR-182-5p.
Affiliations: Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China., School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, China., Department of Nephrology, Second Hospital Lanzhou University Second Hospital, Lanzhou, 730000, Gansu, China., Medical School, Northwest Min Zu University, Lanzhou, 730030, Gansu, China., Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China. .

Abstract:  Background: Accumulating literatures have indicated that long non-coding RNAs (lncRNAs) are potential biomarkers that play key roles in tumor development and progression. Urothelial cancer associated 1 (UCA1) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancers. However, the molecular mechanism of UCA1 in renal cancer is still needed to further explore. Methods: The relative expression level of UCA1 was determined by Real-Time qPCR in a total of 88 patients with urothelial renal cancer and in different renal cancer cell lines. Loss-of-function experiments were performed to investigate the biological roles of UCA1 and miR-182-5p on renal cancer cell proliferation, migration, apoptosis and tumorigenicity. Comprehensive transcriptional analysis, dual-luciferase reporter assay and western blot etc. were performed to explore the molecular mechanisms underlying the functions of UCA1. Results: In this study, we found that UCA1 was significantly up-regulated in renal cancer. Moreover, increased UCA1 expression was positively correlated with differentiation and advanced TNM stage. Further experiments demonstrated that knockdown of UCA1 inhibited malignant phenotypes and Notch signal path of renal cancer cells, and miR-182-5p was reverse function as UCA1. UCA1 functioned as a miRNA sponge to positively regulate the expression of Delta-like ligand 4(DLL4) through sponging miR-182-5p and subsequently promoted malignant phenotypes of renal cancer cells, thus UCA1 playing an oncogenic role and miR-182-5p as an antioncogenic one in renal cancer pathogenesis. Conclusion: UCA1-miR-182-5p-DLL4 axis is involved in proliferation and progression of renal cancer. Thus, this study demonstrated that UCA1 plays a critical regulatory role in renal cancer cell and UCA1 may serve as a potential diagnostic biomarker and therapeutic target of renal cancer. 

Retracted: No

PubPeer comments:
 figure4-A the NC and shUCA1 use the same picture![file] , 
 #1 ![file] Dear Sir Madam, I am very sorry for the inconvenience brought to you. Your carefulness helped us find the mistakes. I have searched the source files in time and found the correct 0H picture(it has been uploaded,https: pubpeer.com storage image-1594915969068.jpg). We very apologize for the inconvenience.I would like to ask you whether we need to contact the magazine to correct it or you have already contacted the magazine. Looking forward to your reply. Thank you! You sincerely Zhongjin Yue , 
 ![file] Figure 6 appears to have an overlapping image , 
 #3 ![file] ![file] Dear Symphyllia Erythraea , I am very sorry for the inconvenience brought to you. Your carefulness helped us find the mistakes. I have searched the source files in time and found the correct ones,and we have revised them. In fact, I can t understand why I made such a mistake,and we often confused images.We very apologize for the inconvenience.I would like to ask you whether we need to contact the magazine to correct it or you have already contacted the magazine again. Thanks! , 
 Figure 3D I d suggest the authors do a thorough check of ALL your figures and prepare for explanations for multiple duplications ![file] ,