Abstract
Long non-coding RNAs (lncRNAs) have been found essential for tumorigenesis of prostate cancer (PC), but its role in the regulation of castration-resistant prostate cancer (CRPC) is poorly identified. Here, we showed that a lncRNA, Breast-Cancer Anti-Estrogen Resistance 4 (BCAR4), which plays a pivotal role in the tamoxifen-resistance of breast cancer, was significantly upregulated in CRPC, but not in castration-sensitive prostate cancer (CSPC), compared to normal prostate tissue. High BCAR4 levels in CRPC were correlated with poor patients’ overall survival. Androgen increased growth and migration of androgen receptor (AR)-positive PC346 cells, which was abolished by the antagonist of androgen. Overexpression of BCAR4 in PC346 cells increased cell growth and migration, but turned the cells insensitive to androgen. On the other hand, growth and migration of AR-negative DU145 cells are insensitive to androgen, while depletion of BCAR4 in DU145 cells not only decreased cell growth, but also turned the cells sensitive again to androgen. Moreover, BCAR4 activated GLI2 downstream genes, and correlated with the levels of these GLI2-target genes in CRPC. Depletion of GLI2 abolished the effects of BCAR4 on cell growth and migration. Together, our data suggest that BCAR4 may activate GLI2 signaling in PC to contribute to castration resistance.
Highlights
Prostate cancer (PC) is a common malignant cancer that affects aged men [1]
We showed that a Long non-coding RNAs (lncRNAs), Breast-Cancer Anti-Estrogen Resistance 4 (BCAR4), which plays a pivotal role in the tamoxifenresistance of breast cancer, was significantly upregulated in castration-resistant prostate cancer (CRPC), but not in castration-sensitive prostate cancer (CSPC), compared to normal prostate tissue
Our data suggest that BCAR4 may activate GLI2 signaling in PC to contribute to castration resistance
Summary
The occurrence and development of PC generally depend on the stimulation of androgen [2]. The local advanced patients, patients with metastatic spread of tumors, and patients who relapse after conventional treatment are currently preferred by clinical endocrine therapy, known as androgen deprivation therapy (ADT) [2]. The stage that responds to endocrine therapy and the response time may vary from person to person due to the tumor heterogeneity, almost all patients eventually develop hormone-independent PC or castration-resistant prostate cancer (CRPC), when more than 90% of the patients will have bone metastasis of primary tumor with concomitant symptoms like severe pain, pathological fractures, spinal compression, and even intracranial nerve disability and anemia [4]. Metastatic CRPC is generally regarded as an incurable disease. It is important to study the molecular mechanisms underlying the development of CRPC, which remains poorly characterized
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