CiRS-7 functions as a ceRNA of RAF-1/PIK3CD to promote metastatic progression of oral squamous cell carcinoma via MAPK/AKT signaling pathways
Authors: Xinjuan Kong
Keqian Zhi
Xiaofei Wang
Jingjing Zheng
Peng Chi
Shaoming Li
Zhichao Dou
Ling Gao
Wenhao Ren
Hao Zhang
Journal: Experimental Cell Research (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Oral squamous cell carcinoma; PIK3CD; RAF-1; ciRS-7; miR-7.
Affiliations: Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266555, Shandong, PR China; School of Stomatology, Qingdao University, Qingdao, 266000, Shandong, PR China., Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266555, Shandong, PR China., Department of Stomatology, People's Hospital, Hubei University of Medicine, Shiyan, 430071, Hubei, PR China., Experiment Center of Biomedical Research, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710049, PR China., Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao, 266555, Shandong, PR China., Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, PR China., Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266555, Shandong, PR China. Electronic address: .

Abstract:  Purpose: Recent Ô¨Åndings have shown that circRNA dysregulation was involved in the development of many types of cancer. However, our knowledge of circRNA in oral squamous cell carcinoma (OSCC) remains elusive. Methods: Here, we explored whether ciRS-7 could function as a ceRNA in promoting metastasis of OSCC via regulating miR-7 activity. The expression levels of ciRS-7 and miR-7 were examined in clinical samples and cell lines by qRT-PCR, and the effects of ectopic expression of ciRS-7 and miR-7 on cell proliferation, migration and invasion were assessed in vitro and in vivo. The effects of ciRS-7 on miR-7 activity were investigated by means of luciferase reporter assay, qRT-PCR and Western blot. In addition, the effects of miR-7 mediated ciRS-7 on the levels of MAPK/AKT signaling proteins were evaluated by Western blot. Results: We found that ciRS-7 was highly expressed in OSCC tissues and cell lines compared with normal counterparts. Ectopic expression of ciRS-7 significantly promoted OSCC cell proliferation, migration and invasion through in vitro and in vivo. Based on bioinformatics analysis, qRT-PCR, Western blot and luciferase reporter assays, we determined that ciRS-7 functioned as a sponge for miR-7, resulting in attenuation of miR-7 targets RAF-1 and PIK3CD, which are core components of the MAPK/AKT signaling pathways. Moreover, miR-7 correlated with perineural and lymphovascular invasion in OSCC patients. Further experiments demonstrated that ciRS-7 overexpression could attenuate the anti-tumor effects of miR-7 on OSCC cells. Conclusions: Our results suggested that ciRS-7 can interact directly with miR-7, resulting in upregulation of RAF-1/PIK3CD expression and enhancing metastatic progression of OSCC. 

Retracted: No

PubPeer comments:
 In Figure 2, the image of two different PCR products presented have been duplicated, modified and presented as something else.  , 
 #1 Dear Sir or Madam, Thanks for your comments on our published article. We have checked the experimental data and confirmed that the experimental results are true and reliable. The main reason for the similar bands is that both bands 1 and 3 are used to detect the expression of ciRS-7 in genomic DNA. We previously put tumor tissue and cell samples in the same gel for the test. The results appeared similar bands is the reason, that there is in the same gel, the same gene, the same molecular weight, the same electrophoresis conditions. We are happy that scholars are paying attention to our articles. ,