ADAR1 promotes the epithelial-to-mesenchymal transition and stem-like cell phenotype of oral cancer by facilitating oncogenic microRNA maturation
Authors: Zhenxing Zhang
Jiadong Huang
Shouwei Zhao
Yu Fu
Xue Liu
Rongyao Xu
Hongbing Jiang
Ping Zhang
Meng Wu
Laikui Liu
Journal: Journal of Experimental & Clinical Cancer Research (2019)
Discipline: CLINICAL MEDICINE
Keywords: ADAR1; Cancer stem cells; Dicer; Epithelial-mesenchymal transition; Oral squamous cell carcinoma
Affiliations: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, No. 136, Hanzhong Road, Nanjing, 210029, Jiangsu Province, China., Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China., Department of Oral Pathology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China., Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, No. 136, Hanzhong Road, Nanjing, 210029, Jiangsu Province, China. .

Abstract:  Background: Adenosine deaminases acting on RNA (ADARs) are involved in adenosine-to-inosine (A-to-I) editing and implicated in tumorigenesis and prognosis. Emerging evidence has indicated that ADAR1, an ADAR family member, participates in the regulation of various cancers; however, its biological function in oral squamous cell carcinoma (OSCC) remains unclear. This study aimed to determine the role of ADAR1 in OSCC progression. Methods: ADAR1 expression in both normal tissues and carcinoma tissues and in OSCC cell lines was examined by real-time PCR and western blotting. Gain-of-function and loss-of-function approaches were used to examine the effect of ADAR1 on the migration, invasion, epithelial-mesenchymal transition (EMT) and stemness of OSCC. Furthermore, the relationship between ADAR1 and Dicer was determined by co-immunoprecipitation, and the expression of OSCC-associated oncogenic miRNAs was evaluated by real-time PCR. For in vivo experiments, a xenograft model where OSCC cells stably expressing ADAR1 were implanted was used to investigate the effect of ADAR1 on tumor growth and progression, and the expression of ADAR1, PCNA, SOX2 and POU5F1 was further detected by immunohistochemistry. The impact of ADAR1 expression on the survival status of OSCC patients was determined by survival analysis. Results: ADAR1 was overexpressed in OSCC and significantly associated with poor patient survival. There was a positive correlation between ADAR1 and the migration, invasion, EMT and stemness of OSCC. Mechanistically, ADAR1 was physically associated with Dicer, and six OSCC-associated oncogenic miRNAs were increased in OSCC cells with ADAR1 overexpression. In the mouse xenograft model of OSCC, ADAR1 overexpression promoted tumor growth and progression. Moreover, ADAR1 was highly expressed in OSCC patients with low survival rates. Conclusions: Our findings demonstrated that ADAR1 may play a significant role in OSCC progression via combining with Dicer to regulate oncogenic miRNA maturation and further affect cell migration and invasion. 

Retracted: No

PubPeer comments:
 ADAR1 antibody from abcam (Ab126755) clearly says it doesnt recognize p110. Although the authors observes and designates p110 in the WB data in Fig1, 3 and 5. , 
 #1 #1 #1 Thank you very much for the editor s valuable comments on this article, making our article more scientific and rigorous Regarding the question  ADAR1 antibody from abcam (Ab126755) clearly says it doesnt recognize p110. Although the authors observes and designates p110 in the WB data in Fig1, 3 and 5 , we carefully reviewed the antibody description and gave the following explanation: 1. The instructions show that the antibody is applied to WB, and detects a band of approximately 110-150 kDa (predicted molecular weight: 136 kDa). 2. The description states in the sequence similarity as followinguff1a Contains 1 A to I editase domain. Contains 2 DRADA repeats. Contains 3 DRBM (double-stranded RNA-binding) domains. The above mentioned domains are the common domains of p110 and 150. [1]It is said that this antibody can act on the common protein domain of both. 3. The repeated experiments using this antibody yielded the same experimental results as described in the article. 1.tSong, B., et al., The role of RNA editing enzyme ADAR1 in human disease. Wiley Interdiscip Rev RNA, 2022. 13(1): p. e1665. ,