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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
miR-488 inhibits cell growth and metastasis in renal cell carcinoma by targeting HMGN5
Xin Wei1, Lili Yu1, Xiangbo Kong1
1Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, China.
Purpose:
microRNAs are thought to play crucial roles in tumorigenesis. Dysregulation of miR-488 has been implicated to be involved in several cancer progressions. However, the biological functions of miR-488 in renal cell carcinoma (RCC) remain unclear. This study aimed to explore the molecular mechanism underlying the role of miR-488 in RCC development.
Materials And Methods:
The expression levels of miR-488 were detected in 38 paired RCC tumor samples and cell lines by quantitative real-time polymerase chain reaction method. miR-488 was upregulated by mimics transfection in RCC cell lines. MTT, colony formation, transwell assay, flow cytometry assay, and a xenograft model were performed to determine cell proliferation, invasion, migration, epithelial-to-mesenchymal transition, and apoptosis in vitro and in vivo. Moreover, the potential target of miR-488 was verified by dual-luciferase reporter assay, quantitative real-time polymerase chain reaction, and Western blot. The correlation between miR-488 expression and its target gene expression was confirmed by Spearman's correlation analysis in 38 selected RCC tissue samples.
Results:
We found that miR-488 was remarkably downregulated in human RCC samples and cell lines compared with paired normal tissues and cell lines. Functional investigations revealed that overexpression of miR-488 significantly suppressed cell proliferation, invasion, and migration, and promoted cell apoptosis in RCC cells. Nucleosome binding protein 1 (high-mobility group nucleosome binding domain 5 [HMGN5]) was identified as a direct target of miR-488, and an inverse relationship was found between miR-488 expression and HMGN5 mRNA levels in RCC specimens. Rescue experiments suggested that restoration of HMGN5 partially abolished miR-488-mediated cell proliferation and invasion inhibition in RCC cells through regulating phosphatidylinositol 3-kinase/protein kinase B/the mammalian target of rapamycin and epithelial-to-mesenchymal transition signaling pathways.
Conclusion:
These data indicated that miR-488 acted as a tumor suppressor in RCC proliferation and invasion by targeting HMGN5, which might provide potential therapeutic biomarker for RCC patients.
Insights
MicroRNA-488 (miR-488) functions as a tumor suppressor in renal cell carcinoma (RCC). It inhibits RCC cell proliferation and invasion by targeting HMGN5, offering a potential therapeutic biomarker for patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are crucial in tumorigenesis.
- Dysregulation of miR-488 is implicated in various cancers.
- The role of miR-488 in renal cell carcinoma (RCC) is not well understood.
Purpose of the Study:
- To investigate the molecular mechanisms of miR-488 in RCC development.
- To explore miR-488's function as a potential tumor suppressor in RCC.
Main Methods:
- Quantitative real-time PCR to measure miR-488 expression in RCC tissues and cell lines.
- In vitro and in vivo assays (MTT, colony formation, transwell, flow cytometry, xenograft) to assess cell proliferation, invasion, migration, apoptosis, and epithelial-to-mesenchymal transition (EMT).
- Dual-luciferase reporter assay, qRT-PCR, and Western blot to identify and validate miR-488 targets, specifically HMGN5.
Main Results:
- miR-488 was significantly downregulated in RCC tissues and cell lines.
- Overexpression of miR-488 suppressed RCC cell proliferation, invasion, and migration, while promoting apoptosis.
- HMGN5 was identified as a direct target of miR-488, with an inverse correlation in RCC specimens.
- HMGN5 restoration partially reversed miR-488's inhibitory effects on proliferation and invasion via PI3K/AKT/mTOR and EMT pathways.
Conclusions:
- miR-488 acts as a tumor suppressor in RCC by targeting HMGN5.
- This interaction inhibits RCC cell proliferation and invasion.
- miR-488 may serve as a potential therapeutic biomarker for RCC.
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