MicroRNA-196-5p targets Derlin-1 to induce autophagy in human osteosarcoma cells
Zhenzhong Ji1, Wei Chen2, Song Wan2
1Department of Orthopedics, Wuhan Puren Hospital, Puren Hospital Affiliated of Wuhan University of Science and Technology, Wuhan, Hubei, 430080, Chinam.
Abstract:
Osteosarcoma is a highly prevalent type of primary bone tissues in children and young adolescents. Micro-RNA (miR) dysregulation has been linked to osteosarcoma tumorigenesis. The role of miR-196-5p was investigated in modulating the growth and metastatic behaviour of human osteosarcoma cells, along with exploring its mechanism of action. As shown by RT-qPCR expression analysis, osteosarcoma cell lines exhibited prominent (P<0.05) transcriptional repression of miR-196-5p. The latter was thus transiently overexpressed in osteosarcoma cells, which resulted in the loss of cell viability and colony formation via induction of autophagy. The western blot analysis of the autophagy marker proteins revealed that the expression of Beclin 1 and LC3B II proteins was induced by miR-196-5p, whereas that of p62 and LC3BI was repressed. Moreover, osteosarcoma cells overexpressing miR-196-5p showed significantly (P<0.05) lower migration and invasion concerning the control osteosarcoma cells. According to the results of the in-silico analysis, Derlin-1 participates in the regulation of miR-196-5p in osteosarcoma, and this prediction has been validated using a dual luciferase assay. The results indicated that miR-196-5p exerted its molecular role by targeting Derlin-1 at the post-transcriptional level. Summing up, the study revealed the modulatory potential of miR-196-5p/Derlin-1 on osteosarcoma cells and provided insights into the possible implications for the treatment and prognosis of the disease.
Insights
MicroRNA-196-5p (miR-196-5p) suppresses osteosarcoma growth and metastasis by inducing autophagy and targeting Derlin-1. This finding offers new insights into osteosarcoma treatment and prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma is a common bone cancer in children and adolescents.
- MicroRNA (miRNA) dysregulation is implicated in osteosarcoma development.
- The specific role of miR-196-5p in osteosarcoma requires further elucidation.
Purpose of the Study:
- To investigate the function of miR-196-5p in human osteosarcoma cells.
- To explore the underlying molecular mechanisms, including its effect on cell viability, autophagy, and metastasis.
- To identify potential molecular targets of miR-196-5p in osteosarcoma.
Main Methods:
- RT-qPCR to assess miR-196-5p expression levels.
- Transient overexpression of miR-196-5p in osteosarcoma cell lines.
- Western blot analysis to evaluate autophagy marker proteins (Beclin 1, LC3B II, p62, LC3BI).
- In-silico analysis and dual-luciferase reporter assays to validate the interaction between miR-196-5p and Derlin-1.
Main Results:
- Osteosarcoma cells showed significantly reduced miR-196-5p expression.
- Overexpression of miR-196-5p led to decreased cell viability and colony formation by inducing autophagy.
- miR-196-5p overexpression significantly reduced cell migration and invasion.
- Derlin-1 was identified as a direct target of miR-196-5p in osteosarcoma cells.
Conclusions:
- miR-196-5p plays a crucial role in suppressing osteosarcoma cell growth and metastasis.
- The miR-196-5p/Derlin-1 axis is a key regulatory pathway in osteosarcoma.
- Targeting miR-196-5p or its downstream effectors may offer therapeutic strategies for osteosarcoma.
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