Abstract
Accumulating evidences have indicated that aberrant expression of long non-coding RNAs (LncRNAs) is tightly associated with cancer development. Previous studies have reported that lncRNA XIST regulates tumor malignancies in several cancers. However, the underlying mechanism of XIST in prostate cancer remains unclear. In the current study, we found that XIST was down-regulated in prostate cancer specimens and cell lines. Low expression of XIST was correlated with poor prognosis and advanced tumor stage in prostate cancer patients. In gain and loss of function assays, we confirmed that XIST suppressed cellular proliferation and metastasis in prostate cancer both in vitro and in vivo. Furthermore, we found that XIST negatively regulates the expression of miR-23a and subsequently promotes RKIP expression at post-transcriptional level. Consequently, we investigated the correlation between XIST and miR-23a, and identified miR-23a as a direct target of XIST. In addition, over-expression of miR-23a efficiently abrogated the up-regulation of RKIP induced by XIST, suggesting that XIST positively regulates the expression of RKIP by competitively binding to miR-23a. Taken together, our study indicated that lncRNA XIST acts as a tumor suppressor in prostate cancer, and this regulatory effect of XIST will shed new light on epigenetic diagnostics and therapeutics in prostate cancer.
Highlights
Prostate cancer (PCa) is the most common malignancy in males, accounting for 15% of the cancers diagnosed in men and 13% of cancer-related deaths [1]
long noncoding RNAs (LncRNAs) XIST is low expressed in prostate cancer tissues and cell lines To determine the role of long non-coding RNA (lncRNA) XIST in different cancers, we explored the expression of XIST in the TCGA data portal from Starbase ver2.0
The results revealed that XIST expression was significantly down-regulated in prostate cancer tissues compared to normal tissues (Figure 1C) and negatively correlated with the metastasis of prostate cancer (Figure 1B)
Summary
Prostate cancer (PCa) is the most common malignancy in males, accounting for 15% of the cancers diagnosed in men and 13% of cancer-related deaths [1]. It has been elucidated that tumor growth in early-stage prostate cancer requires the presence of androgens [2]. Androgen deprivation therapy (ADT) has been the main treatment used for androgen-dependent prostate cancer (ADPC) since 1940, tumors tend to relapse after a remission stage of approximately 18-24 months, and grow in an androgen-independent manner [3, 4]. The mechanism underlying androgen-independent prostate cancer (AIPC) development remains unclear, and AIPC related biomarkers are limited. It is vitally important for us to explore new, detailed signaling pathway in AIPC and determine novel effective molecular biomarkers. As the human genome project has revealed, only 2% of our genome is protein-coding genes, while the rest of the genome is actively transcribed as non-coding www.impactjournals.com/oncotarget
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