Researchers at the University of Tokyo in Japan have shown that a long non-coding RNA (lncRNA) called a suppressor of cytokine signaling 2-antisense transcript 1 (SOCS2-AS1) may be involved in prostate cancer development by impairing cell death.
lncRNAs are RNA molecules that do not code for a protein but are implicated in a variety of processes.
The androgen receptor (AR) and its signaling pathway have been shown to have a major role in the development and progression of both localized and advanced prostate cancer. In addition to surgery and radiotherapy, patients with high-risk localized prostate cancer are often treated with androgen deprivation therapies. However, most prostate cancers escape from androgen dependence and become what is known as castration-resistant prostate cancer (CRPC), revealing the need to identify the players in androgen receptor signaling to develop new targeted therapies.
A number of lncRNAs have been linked with prostate cancer, including PCA3, PCGEM1, PCAT-1, and CTBP1-AS.
CTBP1-AS, particularly, was described by researchers as an androgen-responsive lncRNA that promoted cancer progression.
The researchers aimed at exploring other androgen-dependent lncRNAs that could have roles in prostate cancer progression. They used two prostate cancer cell lines and their corresponding castration-resistant cell lines, and examined their RNA expression with or without androgen treatment.
Among the 11 lncRNAs whose expression was androgen-dependent in both cell lines, SOCS2-AS1 was found to be highly expressed in the castration-resistant cell lines.
To examine the role of SOCS2-AS1, the researchers used small interference RNAs designed to decrease SOCS2-AS1 levels, as well as cell lines overexpressing SOCS2-AS1. Their results demonstrated that SOCS2-AS1 overexpression promoted castration-resistant and androgen-dependent cell growth and migration, whereas decreasing SOCS2-AS1 levels inhibited the growth of both the CRPC cell models and their parental cell lines.
SOCS2-AS1 was also found to regulate the expression of genes involved in a number of pathways linked to cancer progression. TNFSF10, known to mediate cell death, was found to be decreased by SOCS2-AS1.
On the other hand FOXM1, a protein involved in the regulation of cell growth, DNA damage, drug resistance, and metastasis, was induced by SOCS2-AS1.
Together, these findings indicate that SOCS2-AS1 may play an important role in the development of castration-resistant prostate cancer and may be a useful target for future RNA-based therapies.
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