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miR-888 is an expressed prostatic secretions-derived microRNA that promotes prostate cell growth and migration
Holly Lewis1, Raymond Lance2, Dean Troyer1
1Department of Microbiology & Molecular Cell Biology; Leroy T. Canoles Jr. Cancer Research Center; Eastern Virginia Medical School; Norfolk, VA USA.
Abstract:
MicroRNAs (MiRNAs) are a growing class of small non-coding RNAs that exhibit widespread dysregulation in prostate cancer. We profiled miRNA expression in syngeneic human prostate cancer cell lines that differed in their metastatic potential in order to determine their role in aggressive prostate cancer. miR-888 was the most differentially expressed miRNA observed in human metastatic PC3-ML cells relative to non-invasive PC3-N cells, and its levels were higher in primary prostate tumors from cancer patients, particularly those with seminal vesicle invasion. We also examined a novel miRNA-based biomarker source called expressed prostatic secretions in urine (EPS urine) for miR-888 expression and found that its levels were preferentially elevated in prostate cancer patients with high-grade disease. These expression studies indicated a correlation for miR-888 in disease progression. We next tested how miR-888 regulated cancer-related pathways in vitro using human prostate cancer cell lines. Overexpression of miR-888 increased proliferation and migration, and conversely inhibition of miR-888 activity blocked these processes. miR-888 also increased colony formation in PC3-N and LNCaP cells, supporting an oncogenic role for this miRNA in the prostate. Our data indicates that miR-888 functions to promote prostate cancer progression and can suppress protein levels of the tumor suppressor genes RBL1 and SMAD4. This miRNA holds promise as a diagnostic tool using an innovative prostatic fluid source as well as a therapeutic target for aggressive prostate cancer.
Insights
MicroRNAs (miRNAs) promote aggressive prostate cancer by increasing cell proliferation and migration. MiR-888, found in expressed prostatic secretions, shows promise as a diagnostic marker and therapeutic target for advanced prostate cancer.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs with significant roles in gene regulation.
- Dysregulation of miRNAs is frequently observed in various cancers, including prostate cancer.
- Understanding miRNA roles is crucial for developing novel diagnostic and therapeutic strategies.
Purpose of the Study:
- To investigate the role of specific microRNAs in prostate cancer progression and metastasis.
- To identify potential miRNA biomarkers in expressed prostatic secretions for prostate cancer diagnosis.
- To explore miR-888 as a therapeutic target for aggressive prostate cancer.
Main Methods:
- Profiling miRNA expression in human prostate cancer cell lines with varying metastatic potential.
- Quantifying miR-888 levels in patient tumor samples and expressed prostatic secretions (EPS) in urine.
- In vitro functional assays to assess the impact of miR-888 on cancer cell proliferation, migration, and colony formation.
Main Results:
- miR-888 was significantly upregulated in metastatic prostate cancer cells and primary tumors with seminal vesicle invasion.
- Elevated miR-888 levels were detected in EPS urine of patients with high-grade prostate cancer, correlating with disease progression.
- Overexpression of miR-888 enhanced prostate cancer cell proliferation, migration, and colony formation, while inhibition reversed these effects.
- miR-888 was found to suppress the tumor suppressor genes RBL1 and SMAD4.
Conclusions:
- miR-888 acts as an oncogenic microRNA, promoting prostate cancer progression and aggressiveness.
- miR-888 in EPS urine represents a promising, non-invasive biomarker for diagnosing high-grade prostate cancer.
- Targeting miR-888 offers a potential therapeutic strategy for aggressive prostate cancer.
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