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Published on: March 30, 2019
miRNA-331-3p Affects the Proliferation, Metastasis, and Invasion of Osteosarcoma through SOCS1/JAK2/STAT3
Dan Zu1, Qi Dong2, Sunfang Chen2
1Central Laboratory, The Central Hospital, Shaoxing University, Shaoxing 312030, China.
Abstract:
MicroRNAs (miRNAs) are regulatory small noncoding RNAs that play a key role in several types of cancer. It has been reported that miR-331-3p is involved in the development and progression of various cancers, but there are few reports regarding osteosarcoma (OS). The public GEO database was used to analyze the survival difference of miR-331-3p in OS organizations. The level of cell proliferation assay was assessed by CCK-8 and colony formation. First, transwell and wound-healing assays were used to detect the transfer and invasion ability of miR-331-3p in OS. Second, TargetScan, miRDBmiR, TarBase, and dual-luciferase reporter gene assays were used to determine SOCS1 as a targeted regulator. Third, Western blot and immunohistochemistry were used to detect the expression of protein levels. Finally, a mouse model of subcutaneously transplantable tumors is used to evaluate the proliferation of OS in vivo. The low expression of miR-331-3p was negatively correlated with the overall survival of OS patients. Overexpression of miR-331-3p significantly inhibited cell proliferation, metastasis, and invasion. Moreover, miR-331-3p affected the occurrence and development of osteosarcoma by targeting the SOCS1/JAK2/STAT3 signaling pathway. Therefore, miR-331-3p reduces the expression of SOCS1 by combining with its 3'UTR, thereby activating the JAK2/STAT3 signaling pathway to regulate the progression of OS. This provides a new theoretical basis for the treatment of osteosarcoma.
Insights
Low expression of microRNA-331-3p (miR-331-3p) correlates with poor survival in osteosarcoma patients. Upregulating miR-331-3p inhibits cancer cell growth and metastasis by targeting the SOCS1/JAK2/STAT3 pathway.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are crucial regulators in cancer development.
- miR-331-3p's role in osteosarcoma (OS) is under-investigated.
- Existing research suggests miR-331-3p involvement in various cancers.
Purpose of the Study:
- To investigate the role and mechanism of miR-331-3p in osteosarcoma.
- To analyze the correlation between miR-331-3p expression and patient survival.
- To elucidate the molecular targets and pathways regulated by miR-331-3p in OS.
Main Methods:
- Analysis of public GEO database for survival data.
- Cell proliferation, migration, and invasion assays (CCK-8, colony formation, Transwell, wound-healing).
- Bioinformatic prediction (TargetScan, miRDBmiR, TarBase) and luciferase reporter assays to identify miR-331-3p targets.
- Western blot, immunohistochemistry, and in vivo mouse models to validate findings.
Main Results:
- Low miR-331-3p expression is linked to decreased overall survival in osteosarcoma patients.
- Overexpression of miR-331-3p significantly suppressed osteosarcoma cell proliferation, migration, and invasion.
- miR-331-3p was identified as a direct regulator of SOCS1, impacting the JAK2/STAT3 signaling pathway.
Conclusions:
- miR-331-3p acts as a tumor suppressor in osteosarcoma.
- The miR-331-3p/SOCS1/JAK2/STAT3 axis is a key regulator of osteosarcoma progression.
- miR-331-3p represents a potential therapeutic target for osteosarcoma treatment.
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