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Published on: June 12, 2019
MiR-99a exerts anti-metastasis through inhibiting myotubularin-related protein 3 expression in oral cancer
1Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Objective:
We aimed at studying the role of the most deregulated miR-99a, identifying its downstream targets, and exploring the clinical potential of miR-99a and its target(s) in oral cancer.
Subjects And Methods:
Following confirmation of miR-99a deregulation in nine oral lines and 26 pairwise clinical specimens, miR-99a-manipulated oral cancer cells were subjected to cell proliferation, migration, invasion, and in vivo murine metastasis assays. We characterized putative miR-99a target(s) using luciferase reporter assays and genetic manipulation. The inverse relation of miR-99a and its target(s) was examined in clinical specimens using real-time PCR and Western blot analysis.
Results:
MiR-99a down-regulation was confirmed both in tested oral cancer cell lines and clinical specimens. Ectopic miR-99a expression inhibited oral cancer cell migration and invasion. Anti-miR-99a, silencing miR-99a functions, had the opposite effect. Myotubularin-related protein 3 (MTMR3) with one evolutionarily conserved seed region in the 3'-untranslated region was a novel miR-99a target. Depleting MTMR3 expression significantly reduced cell proliferation, migration, or invasion. There was an inverse expression of miR-99a and MTMR3 protein in oral cancer lines and clinical specimens.
Conclusion:
miR-99a repressed oral cancer cell migration and invasion partly through decreasing MTMR3 expression. MTMR3 may serve as a therapeutic target for oral cancer treatment.
Insights
MicroRNA-99a (miR-99a) down-regulation promotes oral cancer progression by increasing Myotubularin-related protein 3 (MTMR3). Targeting MTMR3 offers a potential therapeutic strategy for oral cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Oral cancer is a significant global health concern.
- MicroRNAs (miRNAs) play crucial roles in cancer development and progression.
- Dysregulation of specific miRNAs, like miR-99a, is implicated in various cancers.
Purpose of the Study:
- To investigate the role of deregulated miR-99a in oral cancer.
- To identify downstream targets of miR-99a.
- To explore the clinical potential of miR-99a and its targets in oral cancer treatment.
Main Methods:
- Confirmation of miR-99a deregulation in oral cancer cell lines and clinical specimens.
- Functional assays including cell proliferation, migration, invasion, and metastasis.
- Identification of miR-99a targets using luciferase reporter assays and genetic manipulation.
- Analysis of inverse miR-99a and target expression in clinical samples via real-time PCR and Western blot.
Main Results:
- miR-99a was consistently down-regulated in oral cancer.
- Restoring miR-99a expression inhibited oral cancer cell migration and invasion.
- Myotubularin-related protein 3 (MTMR3) was identified as a novel, evolutionarily conserved target of miR-99a.
- Silencing MTMR3 reduced oral cancer cell proliferation, migration, and invasion.
- An inverse correlation between miR-99a and MTMR3 protein expression was observed in oral cancer.
Conclusions:
- miR-99a suppresses oral cancer cell migration and invasion, partly by down-regulating MTMR3.
- MTMR3 represents a potential therapeutic target for oral cancer intervention.
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