已发表论文

CircRNA CDR1as/miR-7 信号促进骨肉瘤的肿瘤生长,具有潜在的治疗和诊断价值

 

Authors Xu B, Yang T, Wang Z, Zhang Y, Liu S, Shen M

Received 25 June 2018

Accepted for publication 11 August 2018

Published 23 October 2018 Volume 2018:10 Pages 4871—4880

DOI https://doi.org/10.2147/CMAR.S178213

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Professor Nakshatri

Background: The circular RNA (circRNA) antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as)/micro RNA-7(miR-7) signal axis has been investigated in many diseases via regulation of the target genes of miR-7, which participates in the carcinogenesis and metastasis. However, the clinical role and function of CDR1as/miR-7 pathway in osteosarcoma (OS) remain to be identified.
Materials and methods: Noncancerous bone tissues (n=18) and OS tissues (n=38) were used to determine the expressions and roles of CDR1as and miR-7. We knocked down the expression of CDR1as via siRNAs in OS cell lines to analyze its function in vitro and in vivo.
Results: CDR1as was upregulated in OS tissues with significant diagnostic value (cutoff value: 1.613). OS patients with high tumor size, Enneking stage, and distant metastasis have high CDR1as levels, but the miR-7 as tumor suppressor negatively correlated with CDR1as. Inhibition of CDR1as in OS cell lines U2OS and MG63 with high CDR1as levels, leading to de-repressed miR-7 levels, impaired cell vitality and increased apoptosis and G1/S arrest in parallel with reduced ability of cell migration, which, however, could be restored by miR-7 inhibitor. Mechanistically, knockdown of CDR1as could restore the availability of miR-7 and inhibit the target genes of miR-7 including EGFR CCNE1 PI3KCD , and RAF1 . Moreover, CDR1as also upregulated N-cadherin and inhibited E-cadherin to promote the epithelial–mesenchymal transition via miR-7 for cell migration. CDR1as inhibition in vivo also induced tumor regression with decreased PCNA levels, and miR-7 inhibitor could reverse these effects via upregulation of EGFR CCNE1 PI3KCD , and RAF1 . The expressions of these genes were confirmed to be higher in CDR1as-high OS samples than in CDR1as-low OS samples.
Conclusion: These findings suggested that the CDR1as/miR-7 signal axis could be the molecular target for the treatment of OS.
Keywords: CDR1as, miR-7, osteosarcoma, apoptosis, EMT




Figure 6 Knockdown of CDR1as inhibits tumor growth via miR-7 signals.