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MicroRNA-21 Down-regulates Rb1 Expression by Targeting PDCD4 in Retinoblastoma
Fengmei Shen1, Meng-Hsuan Mo2, Liang Chen2
11. Department of Ophthalmology, Xi'an Jiaotong University First Affiliated Hospital, Xi'an, China.
Abstract:
Retinoblastoma (RB) is a children's ocular cancer caused by mutated retinoblastoma 1 (Rb1) gene on both alleles. Rb1 and other related genes could be regulated by microRNAs (miRNA) via complementarily pairing with their target sites. MicroRNA-21 (miR-21) possesses the oncogenic potential to target several tumor suppressor genes, including PDCD4, and regulates tumor progression and metastasis. However, the mechanism of how miR-21 regulates PDCD4 is poorly understood in RB. We investigated the expression of miRNAs in RB cell lines and identified that miR-21 is one of the most deregulated miRNAs in RB. Using qRT-PCR, we verified the expression level of several miRNAs identified by independent microarray assays, and analyzed miRNA expression patterns in three RB cell lines, including Weri-Rb1, Y79 and RB355. We found that miR-19b, -21, -26a, -195 and -222 were highly expressed in all three cell lines, suggesting their potential role in RB tumorigenesis. Using the TargetScan program, we identified a list of potential target genes of these miRNAs, of which PDCD4 is one the targets of miR-21. In this study, we focused on the regulatory mechanism of miR-21 on PDCD4 in RB. We demonstrated an inverse correlation between miR-21 and PDCD4 expression in Weri-Rb1 and Y79 cells. These data suggest that miR-21 down-regulates Rb1 by targeting PDCD4 tumor suppressor. Therefore, miR-21 could serve as a therapeutic target for retinoblastoma.
Insights
MicroRNA-21 (miR-21) is highly expressed in retinoblastoma (RB) and down-regulates the PDCD4 tumor suppressor. This suggests miR-21 is a potential therapeutic target for treating pediatric RB cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Retinoblastoma (RB) is a pediatric eye cancer linked to the retinoblastoma 1 (Rb1) gene.
- MicroRNAs (miRNAs) can regulate tumor suppressor genes, influencing cancer progression.
- The specific role of miR-21 in regulating PDCD4 within RB remains unclear.
Purpose of the Study:
- To investigate the expression patterns of miRNAs in RB cell lines.
- To elucidate the regulatory mechanism of miR-21 on the PDCD4 gene in RB.
- To assess the potential of miR-21 as a therapeutic target for retinoblastoma.
Main Methods:
- Microarray analysis and qRT-PCR were used to determine miRNA expression levels in RB cell lines (Weri-Rb1, Y79, RB355).
- Bioinformatic tools (TargetScan) predicted potential miRNA targets.
- Correlation analysis was performed to assess the relationship between miR-21 and PDCD4 expression.
Main Results:
- Several miRNAs, including miR-19b, -21, -26a, -195, and -222, were highly expressed in all tested RB cell lines.
- miR-21 was identified as a potential regulator of the PDCD4 tumor suppressor gene.
- An inverse correlation between miR-21 and PDCD4 expression was observed in Weri-Rb1 and Y79 cells.
Conclusions:
- miR-21 is significantly deregulated in retinoblastoma.
- miR-21 likely down-regulates the PDCD4 tumor suppressor in RB.
- Targeting miR-21 presents a potential therapeutic strategy for retinoblastoma.
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