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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
[MiR-21 targets PDCD4 to regulate proliferation, apoptosis, and invasion of osteosarcoma MG63 cells]
Zhipeng Wang1, Ziru Zhang1, Jian Zhao2
1Department of Orthopedics, Tangdu Hospital, Air Force Medical University, Xi'an 710038, China.
Abstract:
Objective MicroRNAs (miRNAs) are small endogenous single-stranded non-coding RNAs, approximately 20-25 nucleotides in length, that regulate the expression of potential target mRNAs at the post-transcriptional level. miRNAs are abnormally expressed in many malignant tumors, and are closely associated with tumorigenesis and development, functioning either as proto-oncogenes or oncogenes. Studies have revealed that microRNA-21 (miR-21) is one of the most common oncogenes across various cancer types. However, the function of miR-21 in osteosarcoma has not been fully elucidated. This study aims to investigate the effect of miR-21 on the proliferation, invasion and apoptosis of osteosarcoma cell line MG63 and its underlying mechanisms. Methods Bioinformatics was used to predict the potential target genes of miR-21. The expression levels of miR-21 and programmed cell death 4 (PDCD4) in osteosarcoma cell line MG63 were measured by qRT-PCR and Western blot, respectively. After the expression of miR-21 was regulated (either up-regulated or inhibited), its biological effects on cell viability, cell cycle progression and apoptosis were assessed. The targeting relationship between miR-21 and PDCD4 was verified by using dual-luciferase reporter gene assay. Results Bioinformatics prediction showed that the 3'-UTR region of human PDCD4 gene contained multiple potential miRNA target sites. qRT-PCR results showed that the expression level of miR-21 in the pcDNA3.1-miR-21 group was significantly higher than that in the pcDNA3.1 group and the blank group. Compared with the blank group, up-regulation of miR-21 significantly promoted the proliferation and invasion of osteosarcoma MG63 cells, while inhibiting cell apoptosis. Luciferase reporter gene assay confirmed that PDCD4 was a direct target gene of miR-21, and there was a negative correlation between miR-21 and PDCD4. Conclusion Up-regulation of miR-21 expression promotes proliferation and invasion while inhibiting apoptosis of osteosarcoma cell line MG63 by suppressing the level of endogenous PDCD4. In contrast, down-regulation of miR-21 expression inhibits proliferation and invasion while promoting apoptosis of osteosarcoma cell line MG63. Therefore, miR-21 functions as an oncogene in the development of osteosarcoma and could be a potential therapeutic target.
Insights
MicroRNA-21 (miR-21) promotes osteosarcoma growth and invasion by suppressing programmed cell death 4 (PDCD4). Inhibiting miR-21 could be a therapeutic strategy for osteosarcoma.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry

