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miR-4319 inhibited retinoblastoma cells proliferation, migration, invasion and EMT progress via suppressing CD147
Zhiqing Wu1, Ling Chen1, Chengyue Zhang2
1Department of Ophthalmology, Xi'an Children's Hospital, No. 69, Xijuyuan Road, Lianhu District, Xi'an, 710003, China.
Abstract:
Tumor migration is the critical step that lead to the migration in retinoblastoma (RB), in which microRNAs (miRNAs) play important roles. This study aimed to investigate the role of microRNA-4319 (miR-4319) in the development of retinoblastoma by identifying its targets, as well as its underlying regulatory mechanisms. Our data shown that miR-4319 was downregulated in RB tissues and RB cell lines. Enhanced miR-4319 suppressed cell proliferation, migration, invasion and EMT progress, promoted cell apoptosis in SO-RB50 and RB-Y79 cells. Of note, extracellular matrix metalloproteinase inducer (EMMPRI/CD147) was identified as a direct target gene for miR-4319. MMPs were regulated by CD147 and participated in the miR-4319 regulatory network in SO-RB50 cells. In addition, overexpression of CD147 abrogated the inhibitory effect of miR-4319 on RB cells. In summary, miR-4319 overexpression suppressed cell proliferation, migration and invasion may through suppressing the CD147 mediated MMPs expression, suggesting that miR-4319 may serve as a potential diagnostic biomarker and treatment target for RB.
Insights
MicroRNA-4319 (miR-4319) is downregulated in retinoblastoma (RB). Restoring miR-4319 suppresses tumor growth and metastasis by targeting CD147, offering a potential biomarker and therapeutic target for RB.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tumor migration is a critical factor in retinoblastoma (RB) progression.
- MicroRNAs (miRNAs) are recognized as key regulators in various cancers, including RB.
Purpose of the Study:
- To investigate the role of microRNA-4319 (miR-4319) in retinoblastoma development.
- To identify miR-4319 targets and elucidate its regulatory mechanisms in RB.
Main Methods:
- Quantitative real-time PCR to assess miR-4319 expression in RB tissues and cell lines.
- In vitro functional assays (proliferation, migration, invasion, apoptosis) in RB cell lines (SO-RB50, RB-Y79).
- Bioinformatic analysis and luciferase reporter assays to identify and validate direct targets of miR-4319, focusing on extracellular matrix metalloproteinase inducer (EMMPRI/CD147).
Main Results:
- miR-4319 expression was significantly downregulated in retinoblastoma tissues and cell lines.
- Overexpression of miR-4319 inhibited RB cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while promoting apoptosis.
- Extracellular matrix metalloproteinase inducer (CD147) was identified as a direct target of miR-4319, and its suppression affected matrix metalloproteinases (MMPs) expression.
- Restoration of CD147 expression counteracted the tumor-suppressive effects of miR-4319.
Conclusions:
- miR-4319 functions as a tumor suppressor in retinoblastoma.
- miR-4319 inhibits RB cell proliferation, migration, and invasion, potentially by downregulating CD147 and its downstream MMPs.
- miR-4319 holds promise as a diagnostic biomarker and a therapeutic target for retinoblastoma.
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