Androgen-induced Long Noncoding RNA (lncRNA) SOCS2-AS1 Promotes Cell Growth and Inhibits Apoptosis in Prostate Cancer Cells

Abstract

Long noncoding RNAs (lncRNA) have been associated with the development of cancer. However, the interplay between lncRNAs and androgen receptor (AR) signaling in prostate cancer is still unclear. Here, we identified lncRNAs induced by androgen in AR-positive prostate cancer cells, where induction was abolished by AR knockdown as well as an anti-androgen, bicalutamide. By combining these data, we identified an androgen-regulated lncRNA, suppressor of cytokine signaling 2-antisense transcript 1 (SOCS2-AS1), the expression of which was higher in castration-resistant prostate cancer model cells, i.e. long-term androgen-deprived (LTAD) cells, than in parental androgen-dependent LNCaP cells. SOCS2-AS1 promoted castration-resistant and androgen-dependent cell growth. We found that SOCS2-AS1 knockdown up-regulated genes related to the apoptosis pathway, including tumor necrosis factor superfamily 10 (TNFSF10), and sensitized prostate cancer cells to docetaxel treatment. Moreover, we also demonstrated that SOCS2-AS1 promotes androgen signaling by modulating the epigenetic control for AR target genes including TNFSF10. These findings suggest that SOCS2-AS1 plays an important role in the development of castration-resistant prostate cancer by repressing apoptosis.

LINC00467 promotes cell proliferation and metastasis by binding with IGF2BP3 to enhance the mRNA stability of TRAF5 in hepatocellular carcinoma

“…According to the research conducted concerning cancers in recent decades, HCC has been publicly recognized as a prevalent human malignant tumor with high morbidity, as well as high mortality globally . Accumulating evidence has confirmed that lncRNAs play diverse functional roles in the development of different types of tumors, including colorectal cancer, prostate cancer, gastric cancer, as well as HCC . Although LINC00467 has been shown to be involved in the development of neuroblastoma and lung adenocarcinoma, the regulatory role of LINC00467 in HCC has not been determined.…”

“…For example, lncRNA RP4 regulates colorectal cancer progression by competitively binding with miR‐7‐5p . Androgen‐induced lncRNA SOCS2‐AS1 modulates prostate cancer cell growth, as well as apoptosis . Downregulation of lncRNA‐LOWEG promotes cell invasion in gastric cancer .…”

Current Insights into Long Non-Coding RNAs (LncRNAs) in Prostate Cancer

“…Consequently, high SOCS2-AS1 levels as present in mCRPC possibly contribute to tumourigenesis by promoting anti-apoptotic capabilities of tumour cells (Figure 1C) [87]. Simultaneous blockage of this lncRNA could therefore enhance the efficacy of novel anti-androgens and chemotherapeutics used for mCRPC treatment.…”

Current treatment strategies for advanced prostate cancer

“…74,75 Nakagawa et al reported that there were some patients who experienced negative conversion of AR-V7 in CTCs by treatment with taxanes, suggesting a possibility of re-sensitization from primary resistance to ASIs after taxane therapy. 76 There are some evidence of the interaction between AR signaling and taxanes, including inhibition of AR nuclear localization by taxanes, 69,77,78 AR induced long-non-coding RNA 79 and drug-efflux genes. 80 In addition, it is clear that epigenetic modifications by disease progression affects AR signature leading to tumorgenesis, 81 development of CRPC 82 and drug resistance.…”