CircTET1 Inhibits Retinoblastoma Progression via Targeting miR-492 and miR-494-3p through Wnt/β-catenin Signaling Pathway

ABSTRACT

Purpose: Retinoblastoma (RB) is a frequent intraocular malignancy in children. Circular RNA (circRNA) plays an essential role in regulating the occurrence and development of tumors. This study aimed at investigating the function and molecular basis of hsa_circ_0093996 (circTET1) in RB.

Methods: The expression of circTET1, miR-492 and miR-494-3p was examined using quantitative real-time polymerase chain reaction. Cell proliferation, cycle arrest, apoptosis, migration and invasion of RB cells were detected using Cell Counting Kit-8 (CCK-8), colony formation assay, flow cytometry, scratch assay and transwell analysis, respectively. The levels of matrix metalloproteinase (MMP) 2, MMP9 and Wnt/β-catenin pathway-related proteins were measured via western blot assay. The association between circTET1 and miR-492/miR-494-3p was validated via dual-luciferase reporter assay and RNA pull-down assay. Xenograft assay was employed to analyze tumor growth in vivo.

Results: CircTET1 level was reduced, while miR-492 and miR-494-3p levels were increased in RB tissues and cells. Overexpression of circTET1 inhibited proliferation, migration and invasion, and promoted apoptosis and cell cycle arrest in Y79 and WERI-Rb1 cells. Moreover, circTET1 impeded RB cell progression by sponging miR-492/miR-494-3p. Also, up-regulation of circTET1 restrained Wnt/β-catenin pathway via regulating miR-492 and miR-494-3p. Furthermore, circTET1 suppressed tumor growth in xenograft models.

Conclusion: CircTET1 inhibited RB progression by sponging miR-492/miR-494-3p and inactivating the Wnt/β-catenin pathway, which provided new insights for RB treatment.

KEYWORDS:

• Human retinoblastoma
• circTET1
• miR-492
• miR-494-3p
• Wnt/β-catenin

Highlights

1. CircTET1 was down-regulated in RB tissues and cells.

2. CircTET1 up-regulation impeded RB cell progression.

3. CircTET1 was a sponge of miR-492/miR-494-3p.

4. CircTET1 inhibited Wnt/β-catenin pathway via miR-492/miR-494-3p.

Authors’ contribution

All authors made substantial contribution to conception and design, acquisition of the data, or analysis and interpretation of the data; take part in drafting the article or revising it critically for important intellectual content; gave final approval of the revision to be published; and agree to be accountable for all aspect of the work.

Availability of data and materials

The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

The present study was approved by the ethical review committee of The Affiliated Hospital of China University of Mining and Technology, Xuzhou Eye Research Institute. Written informed consent was obtained from all enrolled patients.

Patient consent for publication

Patients agree to participate.

Additional information

Funding

This work was supported by the key research and development plan of Xuzhou (No.KC19163)