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MicroRNA Detection in Prostate Tumors by Quantitative Real-time PCR qPCR
Published on: May 16, 2012
MicroRNA-939 Directly Targets HDGF to Inhibit the Aggressiveness of Prostate Cancer via Deactivation of the
Jie Situ1, Hao Zhang1, Zi Jin2
1Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China.
Purpose:
MicroRNA-939 (miR-939) has crucial roles in several types of human cancer. However, the expression profile and precise functions of miR-939 in prostate cancer (PCa) are still unclear. This study aimed to determine miR-939 expression in PCa and explore its roles in PCa tumorigenesis.
Methods:
miR-939 expression was determined in PCa tissues and cell lines using reverse transcription-quantitative polymerase chain reaction. Cell Counting Kit-8, colony formation, and flow cytometric assays were used to determine the role of miR-939 in PCa cell proliferation and apoptosis in vitro, whereas a tumor xenograft model was generated to evaluate the effect of miR-939 on tumor growth in vivo. Transwell assays were performed to investigate whether miR-939 affects the migration and invasiveness of PCa cells.
Results:
miR-939 was found to be downregulated in PCa tissues and cell lines, and this downregulation was significantly correlated with tumor stage and lymphatic metastasis. Patients with PCa exhibiting low miR-939 expression had shorter overall survival than those exhibiting high miR-939 expression. Exogenous miR-939 expression suppressed PCa cell proliferation, colony formation, migration, and invasion in vitro; enhanced apoptosis in vitro; and decreased tumor growth in vivo. Investigation of the underlying molecular mechanisms revealed hepatoma-derived growth factor (HDGF) as a direct target gene of miR-939 in PCa. HDGF was found to be significantly upregulated in PCa tissues, and its expression was inversely correlated with miR-939 expression. HDGF silencing and miR-939 upregulation showed similar effects in PCa. Restored HDGF expression counteracted the tumor-suppressive activity of miR-939 overexpression in PCa cells. Furthermore, ectopic miR-939 expression inhibited the WNT/β-catenin pathway activation in PCa both in vitro and in vivo by downregulating HDGF.
Conclusion:
miR-939 functions as a tumor suppressor during PCa tumorigenesis by directly targeting HDGF and deactivating the WNT/β-catenin pathway, suggesting the miR-939/HDGF/WNT/β-catenin pathway as an effective target for PCa therapy.
Insights
MicroRNA-939 (miR-939) acts as a tumor suppressor in prostate cancer (PCa). Its downregulation correlates with poor survival, and restoring miR-939 inhibits PCa growth by targeting HDGF and the WNT/β-catenin pathway.
Area of Science:
- Molecular Oncology
- Cancer Biology
- Gene Regulation
Background:
- MicroRNA-939 (miR-939) plays a role in various human cancers.
- The specific expression and function of miR-939 in prostate cancer (PCa) remain largely unknown.
- Understanding miR-939's role is crucial for developing novel PCa therapies.
Purpose of the Study:
- To investigate the expression profile of miR-939 in PCa tissues and cell lines.
- To elucidate the functional role of miR-939 in PCa tumorigenesis, including proliferation, apoptosis, migration, and invasion.
- To identify the molecular mechanisms underlying miR-939's function in PCa.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (RT-qPCR) for miR-939 expression analysis.
- In vitro assays (Cell Counting Kit-8, colony formation, flow cytometry, Transwell) to assess PCa cell behavior.
- In vivo tumor xenograft models to evaluate tumor growth.
- Western blot and luciferase reporter assays to confirm target gene interactions and pathway modulation.
Main Results:
- miR-939 was significantly downregulated in PCa tissues and cell lines, correlating with advanced tumor stage and metastasis.
- Low miR-939 expression predicted shorter overall survival in PCa patients.
- Overexpression of miR-939 suppressed PCa cell proliferation, migration, invasion, and tumor growth, while promoting apoptosis.
- Hepatoma-derived growth factor (HDGF) was identified as a direct target of miR-939, with its expression inversely correlated with miR-939 levels.
- miR-939 inhibited the WNT/β-catenin pathway by downregulating HDGF.
Conclusions:
- miR-939 functions as a tumor suppressor in PCa by targeting HDGF and inhibiting the WNT/β-catenin pathway.
- The miR-939/HDGF/WNT/β-catenin axis represents a promising therapeutic target for prostate cancer.
- Restoring miR-939 expression may offer a novel strategy for PCa treatment.
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