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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
The lncRNA PCAT29 inhibits oncogenic phenotypes in prostate cancer
Rohit Malik1, Lalit Patel1, John R Prensner1
1Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan. Department of Pathology, University of Michigan, Ann Arbor, Michigan.
Unlabelled:
Long noncoding RNAs (lncRNA) have recently been associated with the development and progression of a variety of human cancers. However, to date, the interplay between known oncogenic or tumor-suppressive events and lncRNAs has not been well described. Here, the novel lncRNA, prostate cancer-associated transcript 29 (PCAT29), is characterized along with its relationship to the androgen receptor. PCAT29 is suppressed by DHT and upregulated upon castration therapy in a prostate cancer xenograft model. PCAT29 knockdown significantly increased proliferation and migration of prostate cancer cells, whereas PCAT29 overexpression conferred the opposite effect and suppressed growth and metastases of prostate tumors in chick chorioallantoic membrane assays. Finally, in prostate cancer patient specimens, low PCAT29 expression correlated with poor prognostic outcomes. Taken together, these data expose PCAT29 as an androgen-regulated tumor suppressor in prostate cancer.
Implications:
This study identifies PCAT29 as the first androgen receptor-repressed lncRNA that functions as a tumor suppressor and that its loss may identify a subset of patients at higher risk for disease recurrence. Visual Overview: http://mcr.aacrjournals.org/content/early/2014/07/31/1541-7786.MCR-14-0257/F1.large.jpg.
Insights
Prostate cancer-associated transcript 29 (PCAT29) is a novel long noncoding RNA (lncRNA) that acts as a tumor suppressor. Low PCAT29 expression indicates a higher risk of prostate cancer recurrence.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) are increasingly implicated in human cancer development and progression.
- The specific roles and interactions of lncRNAs with established oncogenic or tumor-suppressive pathways remain underexplored.
Purpose of the Study:
- To characterize the novel lncRNA, prostate cancer-associated transcript 29 (PCAT29).
- To investigate the relationship between PCAT29 and the androgen receptor signaling pathway in prostate cancer.
Main Methods:
- Prostate cancer xenograft models and chick chorioallantoic membrane assays were utilized.
- PCAT29 expression levels were manipulated (knockdown and overexpression) to assess functional effects.
- Analysis of PCAT29 expression in patient specimens was correlated with clinical outcomes.
Main Results:
- PCAT29 expression is suppressed by dihydrotestosterone (DHT) and upregulated following castration therapy.
- PCAT29 knockdown enhanced prostate cancer cell proliferation and migration.
- PCAT29 overexpression suppressed tumor growth and metastasis in preclinical models.
- Low PCAT29 expression in patient samples correlated with poor prognosis.
Conclusions:
- PCAT29 is identified as an androgen receptor-repressed tumor suppressor lncRNA in prostate cancer.
- Loss of PCAT29 may serve as a biomarker for identifying patients at increased risk of recurrence.
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