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 study, “Androgen-induced lncRNA SOCS2-AS1 Promotes Cell Growth and Inhibits Apoptosis in Prostate Cancer Cells,” was published in The Journal of Biological Chemistry.
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.