scholarly journals The long noncoding RNA H19 regulates tumor plasticity in neuroendocrine prostate cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Neha Singh ◽  
Varune R. Ramnarine ◽  
Jin H. Song ◽  
Ritu Pandey ◽  
Sathish K. R. Padi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Fate ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
De Novo ◽  
Treatment Resistance ◽  
Predictive Marker ◽  
Castration Resistant Prostate Cancer ◽  
Tumor Plasticity ◽  
Degree Of Association

AbstractNeuroendocrine (NE) prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (PCa) arising either de novo or from transdifferentiated prostate adenocarcinoma following androgen deprivation therapy (ADT). Extensive computational analysis has identified a high degree of association between the long noncoding RNA (lncRNA) H19 and NEPC, with the longest isoform highly expressed in NEPC. H19 regulates PCa lineage plasticity by driving a bidirectional cell identity of NE phenotype (H19 overexpression) or luminal phenotype (H19 knockdown). It contributes to treatment resistance, with the knockdown of H19 re-sensitizing PCa to ADT. It is also essential for the proliferation and invasion of NEPC. H19 levels are negatively regulated by androgen signaling via androgen receptor (AR). When androgen is absent SOX2 levels increase, driving H19 transcription and facilitating transdifferentiation. H19 facilitates the PRC2 complex in regulating methylation changes at H3K27me3/H3K4me3 histone sites of AR-driven and NEPC-related genes. Additionally, this lncRNA induces alterations in genome-wide DNA methylation on CpG sites, further regulating genes associated with the NEPC phenotype. Our clinical data identify H19 as a candidate diagnostic marker and predictive marker of NEPC with elevated H19 levels associated with an increased probability of biochemical recurrence and metastatic disease in patients receiving ADT. Here we report H19 as an early upstream regulator of cell fate, plasticity, and treatment resistance in NEPC that can reverse/transform cells to a treatable form of PCa once therapeutically deactivated.

scholarly journals Exosomal Long Noncoding RNA HOXD-AS1 Promotes Prostate Cancer Metastasis via miR-361-5p/FOXM1 Axis

2021 ◽  
Author(s):  
Yongming Jiang ◽  
Hui Zhao ◽  
Yuxiao Chen ◽  
Kangjian Li ◽  
Jianheng Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Distant Metastasis ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Cancer Metastasis ◽  
Specific Antigen ◽  
Luciferase Assay ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival

Abstract Background: Development of distant metastasis is the main cause of deaths in prostate cancer (PCa) patients. Understanding the mechanism of PCa metastasis is of utmost importance to improve its prognosis. The role of exosomal long noncoding RNA (lncRNA) has been reported yet fully understood in the metastasis of PCa. Methods: Co-culture assay, in-situ hybridization and quantitative PCR (qPCR) were applied to identify the presence of HOXD-AS1 overexpressing exosomes secreted by of castration resistant prostate cancer (CRPC) cells. Migration and wound healing assays were carried out to evaluate the biological function of exosomal HOXD-AS1. Then a mouse model was used to elucidate the effect of exosomal HOXD-AS1 on distant metastasis of PCa in vivo. Further RNA immunoprecipitation and luciferase assay were applied to identify the interaction between HOXD-AS1 and miR-361-5p. Moreover, rescue experiment was conducted to prove the binding of exosomal HOXD-AS1 and miR-361-5p. Last but not least, the application of serum exosomal HOXD-AS1 as a diagnostic and prognostic biomarker for PCa was evaluated. Results: We discovered the exosomal lncRNA HOXD-AS1 is upregulated in CRPC cell line derived exosomes and serum exosomes from metastatic PCa patients, which correlated with its tissue expression. Further investigation confirmed exosomal HOXD-AS1 promotes prostate cancer cell metastasis in vitro and in vivo by inducing metastasis associated phenotype. Mechanistically exosomal HOXD-AS1 was internalized directly by PCa cells, acting as competing endogenous RNA (ceRNA) to modulate the miR-361-5p/FOXM1 axis, therefore promoting PCa metastasis. In addition, we found that serum exosomal HOXD-AS1 was upregulated in metastatic PCa patients, especially those with high volume disease. And it is correlated closely with Gleason Score, distant and nodal metastasis, Prostatic specific antigen (PSA) recurrence free survival and progression free survival (PFS). Conclusions: Our study sheds a new insight into the regulation of PCa distant metastasis by exosomal HOXD-AS1 mediated miR-361-5p/FOXM1 axis, and provided a promising liquid biopsy biomarker as well as therapeutic target to the detection and treatment of metastatic PCa.

scholarly journals Imaging of Neuroendocrine Prostatic Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5765
Author(s):  
Ahmed Taher ◽  
Corey T. Jensen ◽  
Sireesha Yedururi ◽  
Devaki Shilpa Surasi ◽  
Silvana C. Faria ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Poor Prognosis ◽  
Prostatic Carcinoma ◽  
De Novo ◽  
Treatment Resistance ◽  
Metastatic Potential ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Neuroendocrine Prostate Cancer ◽  
Aggressive Subtype

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer that typically has a high metastatic potential and poor prognosis in comparison to the adenocarcinoma subtype. Although it can arise de novo, NEPC much more commonly occurs as a mechanism of treatment resistance during therapy for conventional prostatic adenocarcinoma, the latter is also termed as castration-resistant prostate cancer (CRPC). The incidence of NEPC increases after hormonal therapy and they represent a challenge, both in the radiological and pathological diagnosis, as well as in the clinical management. This article provides a comprehensive imaging review of prostatic neuroendocrine tumors.

scholarly journals Exosomal long noncoding RNA HOXD-AS1 promotes prostate cancer metastasis via miR-361-5p/FOXM1 axis

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Yongming Jiang ◽  
Hui Zhao ◽  
Yuxiao Chen ◽  
Kangjian Li ◽  
Tianjie Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Distant Metastasis ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Cancer Metastasis ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival

AbstractDevelopment of distant metastasis is the main cause of deaths in prostate cancer (PCa) patients. Understanding the mechanism of PCa metastasis is of utmost importance to improve its prognosis. The role of exosomal long noncoding RNA (lncRNA) has been reported not yet fully understood in the metastasis of PCa. Here, we discovered an exosomal lncRNA HOXD-AS1 is upregulated in castration resistant prostate cancer (CRPC) cell line derived exosomes and serum exosomes from metastatic PCa patients, which correlated with its tissue expression. Further investigation confirmed exosomal HOXD-AS1 promotes prostate cancer cell metastasis in vitro and in vivo by inducing metastasis associated phenotype. Mechanistically exosomal HOXD-AS1 was internalized directly by PCa cells, acting as competing endogenous RNA (ceRNA) to modulate the miR-361-5p/FOXM1 axis, therefore promoting PCa metastasis. In addition, we found that serum exosomal HOXD-AS1 was upregulated in metastatic PCa patients, especially those with high volume disease. And it is correlated closely with Gleason Score, distant and nodal metastasis, Prostatic specific antigen (PSA) recurrence free survival, and progression free survival (PFS). This sheds a new insight into the regulation of PCa distant metastasis by exosomal HOXD-AS1 mediated miR-361-5p/FOXM1 axis, and provided a promising liquid biopsy biomarker to guide the detection and treatment of metastatic PCa.

scholarly journals Retraction: Long noncoding RNA PCA3 regulates glycolysis, viability and apoptosis by mediating the miR-1/CDK4 axis in prostate cancer

RSC Advances ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 5894-5894
Author(s):  
Laura Fisher
Keyword(s):  
Prostate Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna

Retraction of ‘Long noncoding RNA PCA3 regulates glycolysis, viability and apoptosis by mediating the miR-1/CDK4 axis in prostate cancer’ by Shuo Gu et al., RSC Adv., 2018, 8, 37564–37572, DOI: 10.1039/C8RA08083F

The function of long noncoding RNA HOTAIRM1 in the progression of prostate cancer cells

Andrologia ◽  
2020 ◽  
Author(s):  
Lei Wang ◽  
Longning Wang ◽  
Qingfen Wang ◽  
Bahman Yosefi ◽  
Sen Wei ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Prostate Cancer Cells

scholarly journals Molecular and Functional Links between Neurodevelopmental Processes and Treatment-Induced Neuroendocrine Plasticity in Prostate Cancer Progression

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 692
Author(s):  
Roosa Kaarijärvi ◽  
Heidi Kaljunen ◽  
Kirsi Ketola
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Treatment Resistance ◽  
Research Field ◽  
Phenotypic Change ◽  
Prostate Cancer Progression ◽  
Castration Resistant Prostate Cancer ◽  
Treatment Resistant ◽  
Molecular Features ◽  
Neuroendocrine Prostate Cancer

Neuroendocrine plasticity and treatment-induced neuroendocrine phenotypes have recently been proposed as important resistance mechanisms underlying prostate cancer progression. Treatment-induced neuroendocrine prostate cancer (t-NEPC) is highly aggressive subtype of castration-resistant prostate cancer which develops for one fifth of patients under prolonged androgen deprivation. In recent years, understanding of molecular features and phenotypic changes in neuroendocrine plasticity has been grown. However, there are still fundamental questions to be answered in this emerging research field, for example, why and how do the prostate cancer treatment-resistant cells acquire neuron-like phenotype. The advantages of the phenotypic change and the role of tumor microenvironment in controlling cellular plasticity and in the emergence of treatment-resistant aggressive forms of prostate cancer is mostly unknown. Here, we discuss the molecular and functional links between neurodevelopmental processes and treatment-induced neuroendocrine plasticity in prostate cancer progression and treatment resistance. We provide an overview of the emergence of neurite-like cells in neuroendocrine prostate cancer cells and whether the reported t-NEPC pathways and proteins relate to neurodevelopmental processes like neurogenesis and axonogenesis during the development of treatment resistance. We also discuss emerging novel therapeutic targets modulating neuroendocrine plasticity.

Sign in / Sign up

Export Citation Format

Share Document