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miR-139 inhibits osteosarcoma cell proliferation and invasion by targeting ROCK1
Gentao Fan1, Zhiwei He1, Lili Cao1
1Department of orthopedics, The Jinling Hospital, Nanjing 210002, China.
Abstract:
miR-139 has a tumor suppressor effect in many tumors. Here, we examined the suppressive role of this miRNA and its target, ROCK1, in osteosarcoma (OS), a highly malignant bone tumor that mainly affects children and adolescents. The expression of miR-139 was down-regulated in OS. Overexpression of miR-139 significantly inhibited OS cell proliferation, migration, and invasion. Ectopic expression of miR-139 down-regulated ROCK1, a target of miR-139, by direct binding to its 3' untranslated region (3'UTR). Direct siRNA-mediated silencing of ROCK1 exerted an inhibitory effect on OS cell proliferation and invasion similar to the effect of miR-139. ROCK1 transfection reversed the suppressive effect of miR-139 on OS cell proliferation and invasion. Both miR-139 and siRNA knockdown of ROCK1 significantly down-regulated β-CATENIN and p-AKT and up-regulated E-CADHERIN and p53. The data provided here show that miR-139 exerts suppressive effects on proliferation and invasion of OS cells by targeting ROCK1.
Insights
MicroRNA-139 (miR-139) acts as a tumor suppressor in osteosarcoma (OS) by inhibiting cell proliferation and invasion. It targets ROCK1, a key factor in OS progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNA-139 (miR-139) is recognized for its tumor suppressor functions across various cancers.
- Osteosarcoma (OS) is a prevalent and aggressive bone malignancy primarily affecting pediatric and adolescent populations.
Purpose of the Study:
- To investigate the inhibitory role of miR-139 and its target, ROCK1, in osteosarcoma progression.
- To elucidate the molecular mechanisms underlying miR-139's tumor-suppressive activity in OS cells.
Main Methods:
- Quantitative real-time PCR to assess miR-139 expression levels in OS.
- Cell proliferation, migration, and invasion assays following miR-139 overexpression or ROCK1 knockdown.
- Western blotting to analyze protein expression changes (β-CATENIN, p-AKT, E-CADHERIN, p53).
- Luciferase reporter assays to confirm direct binding of miR-139 to the ROCK1 3'UTR.
Main Results:
- miR-139 expression was significantly downregulated in osteosarcoma tissues.
- Overexpression of miR-139 suppressed OS cell proliferation, migration, and invasion.
- miR-139 directly targeted ROCK1 by binding to its 3' untranslated region (3'UTR).
- Silencing ROCK1 mimicked the inhibitory effects of miR-139 on OS cell behaviors.
- ROCK1 re-expression reversed the suppressive effects of miR-139.
- Both miR-139 and ROCK1 knockdown modulated key signaling pathways, including β-CATENIN, p-AKT, E-CADHERIN, and p53.
Conclusions:
- miR-139 functions as a tumor suppressor in osteosarcoma by targeting ROCK1.
- The miR-139/ROCK1 axis influences critical cellular processes like proliferation and invasion in OS.
- Modulation of the miR-139/ROCK1 pathway impacts downstream signaling molecules involved in cancer progression.
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