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MiR-21 Regulates Growth and Migration of Cervical Cancer Cells by RECK Signaling Pathway
Seidy Y Aguilar-Martínez1, Gabriela E Campos-Viguri1, Selma E Medina-García1
1Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, Instituto Nacional de Salud Pública, Cuernavaca 62100, Mexico.
Abstract:
Expression of miR-21 has been found to be altered in almost all types of cancers, and it has been classified as an oncogenic microRNA. In addition, the expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study, we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells, there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3'-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed, and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.
Insights
MicroRNA-21 (miR-21) promotes cervical cancer cell survival by suppressing the RECK gene. Inhibiting miR-21 reduces cancer cell proliferation and migration, suggesting miR-21 and RECK as potential gene therapy targets.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- MicroRNA-21 (miR-21) is an oncogenic microRNA implicated in various cancers.
- RECK, a tumor suppressor gene, shows altered expression in cervical lesions, inversely correlating with miR-21.
- Understanding miR-21's role in RECK regulation is crucial for cervical cancer research.
Purpose of the Study:
- To investigate the regulatory relationship between miR-21 and the RECK gene in cervical cancer cells.
- To determine the functional impact of miR-21 on RECK expression, cell proliferation, and migration.
Main Methods:
- Silencing endogenous miR-21 using small interfering RNAs (siRNAs).
- Analyzing miR-21 and RECK mRNA and protein expression levels.
- Utilizing luciferase reporter assays with RECK 3'-UTR constructs to confirm miR-21 binding sites.
- Assessing the effects of miR-21 inhibition on cell proliferation and migration.
Main Results:
- An inverse correlation was observed between miR-21 expression and RECK mRNA/protein levels in cervical cancer cells.
- miR-21 inhibition via siRNAs led to increased luciferase activity in constructs containing RECK 3'-UTR response elements.
- Silencing miR-21 significantly reduced cervical cancer cell proliferation and migration.
Conclusions:
- miR-21 post-transcriptionally down-regulates RECK expression in cervical cancer.
- This down-regulation of RECK by miR-21 promotes cancer cell proliferation and migration.
- miR-21 and RECK represent potential therapeutic targets for cervical cancer gene therapy.
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