The Placental Gene PEG10 Promotes Progression of Neuroendocrine Prostate Cancer

Akamatsu, Shusuke; Wyatt, Alexander W.; Lin, Dong; Lysakowski, Summer; Zhang, Fan; Kim, Soojin; Tse, Charan; Wang, Kendric; Mo, Fan; Haegert, Anne; Brahmbhatt, Sonal; Bell, Robert H.; Adomat, Hans; Kawai, Yosuke; Xue, Hui; Dong, Xin; Fazli, Ladan; Tsai, Harrison; Lotan, Tamara L.; Kossaï, Myriam; Mosquera, Juan Miguel; Rubin, Mark A.; Beltran, Himisha; Zoubeidi, Amina; Wang, Yuzhuo; Gleave, Martin; Collins, Colin C.

doi:10.1016/j.celrep.2015.07.012

Cited by 239 publications

(280 citation statements)

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“…Recently, we successfully developed the first-in-field patient tissue-derived xenograft model of complete NEPC trans-differentiation from prostate adenocarcinoma [36,52]. To identify the mechanisms of NEPC initiation, we conducted transcriptomic and genomic analyses on our ADT-induced NEPC model (LTL-331R) and on its hormone-sensitive predecessor (LTL-331).…”

Section: The Epigenetic/non-coding Interactome and Its Implication Inmentioning

confidence: 99%

The Role of Epigenetics and Long Noncoding RNA MIAT in Neuroendocrine Prostate Cancer

et al. 2016

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Neuroendocrine prostate cancer (NEPC) is the most lethal prostatic neoplasm.NEPC is thought to originate from the trans-differentiation of AR-positive adenocarcinoma cells. We have previously shown that an epigenetic/non-coding interactome (ENI) orchestrates cancer cells' plasticity, thereby allowing the emergence of metastatic, drugresistant neoplasms. The primary objective of this manuscript is to discuss evidence indicating that some components of the ENI (Polycomb genes, microRNAs) play a key role in NEPC initiation and progression. Long non-coding RNAs (lncRNAs) represent vast and largely unexplored component of the ENI. Their role in NEPC has not been investigated. We show preliminary evidence indicating that a lncRNA (MIAT) is selectively up-regulated in NEPCs and might interact with Polycomb genes. Our results indicate that lncRNAs can be exploited as new biomarkers and therapeutic targets for NEPC.Keywords: Neuroendocrine prostate cancer; MIAT; Long non-coding RNAs; Polycomb; Epigenetic/non-coding interactome; Trans-differentiation. Neuroendocrine Prostate Cancer: Clinical and Molecular FeaturesIn adult males, the prostate is a small acorn-shaped tissue with ductal-acinar histology surrounding the urethra at the base of the bladder. Its main function is to contribute secretory proteins to the seminal fluid [1]. The adult prostate is a pseudo-stratified epithelium composed of three main cell lineages (Fig.1, left panel): 1) secretory luminal cells are the predominant cell type; these cells express keratins (K8, K18), the androgen receptor (AR) and secretory proteins such as prostate-specific antigen (PSA) and prostatic specific acid phosphatase (PSAP);2) basal cells expressing K5 and K14 keratins and p63 are the second major cell type;3) neuroendocrine cells (NEC) expressing chromogranin A (CHGA), synaptophysin (SYP), and neuropeptides are scattered throughout the basal layer and comprise less than 1% of normal prostatic glandular epithelium [1][2][3].Prostate cancer (PCa) represents the second most frequently diagnosed neoplasm and is the sixth leading cause of cancer-related deaths in males worldwide [4,5]. In keeping with the composition of prostate epithelium, more than 95% of PCas are classified as adenocarcinomas, which show luminal phenotype and AR expression [6] (Fig.1, middle panel).Endogenous androgens, mainly produced by the testis, bind to the AR and fuel prostate adenocarcinoma proliferation [7]. For this reason, androgen-deprivation therapy (a.k.a. castration) is an effective therapeutic strategy for this disease. However, patients invariably relapse despite castrate androgen levels (castration-resistant PCa, CRPC) mainly via genetic and epigenetic alterations that facilitate ligand-independent AR activation, amplify the ARdependent signaling, or trigger different proliferative pathways [7]. CRPCs are characterized by substantially worse prognoses, but chemotherapeutics and newly approved hormonal treatments (e.g., Enzalutamide [8] and Abiraterone [9]) are still effective in p...

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Section: The Epigenetic/non-coding Interactome and Its Implication Inmentioning

confidence: 99%

The Role of Epigenetics and Long Noncoding RNA MIAT in Neuroendocrine Prostate Cancer

et al. 2016

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“…Akamatsu et al have reported that PEG10 was highly expressed in neuroendocrine prostate cancer (NEPC), and distinct isoforms of PEG10 promoted proliferation and invasion of NEPC cells, which could be recognized as a specific therapeutic target for NEPC (12). Abnormal overexpression of PEG10 was found in most hepatocellular carcinoma cells, and regenerating mouse liver cells (13).…”

Section: Introductionmentioning

confidence: 99%

PEG10 promotes human breast cancer cell proliferation, migration and invasion

Xiao

Tembo

et al. 2016

International Journal of Oncology

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Abstract. Paternally expressed imprinted gene 10 (PEG10), derived from the Ty3/Gypsy family of retrotransposons, has been implicated as a genetic imprinted gene. Accumulating evidence suggests that PEG10 plays an important role in tumor growth in various cancers, including hepatocellular carcinoma, lung cancer and prostate cancer. However, the correlation between PEG10 and breast cancer remains unclear.In the present study, we evaluated and characterized the role of PEG10 in human breast cancer proliferation, cell cycle, clone formation, migration and invasion. The expression level of PEG10 was significantly elevated in breast cancer tissues and associated with distant metastasis and poor clinical outcome. Gene set enrichment analysis indicated that high expression of PEG10 could enrich cell cycle-related processes in breast cancer tissues. Ectopic overexpression of PEG10 in breast cancer cells enhanced cell proliferation, cell cycle, clone formation along with migration and invasion. Cell-to-cell junction molecule E-cadherin was downregulated and matrix degradation proteases MMP-1, MMP-2, MMP-9 were up regulated after PEG10 overexpression. Our results demonstrated that PEG10 is a crucial oncogene and has prognostic value for breast cancer, which could be applied in breast cancer diagnosis and targeting therapy in future.

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“…Regarding prediction of NF1 inactivated tumors, we observed several genes that have been linked to cancer such as QPRT, which is highly expressed in malignant pheochromocytomas as compared to benign; RSL1D1 (CSIG), which stabilizes c-myc in hepatocellular carcinoma; PPEF, which is highly expressed in astrocytic gliomas as compared to normal brain tissue [50][51][52]; and PEG10, a poor prognostic marker and regulator of proliferation, migration, and invasion in several tumor types [53][54][55]. We also observed ATF5, a gene for which expression in malignant glioma is correlated with poor survival [56].…”

Section: Discussionmentioning

confidence: 99%

A machine learning classifier trained on cancer transcriptomes detects NF1 inactivation signal in glioblastoma

Way

Allaway

Bouley

et al. 2016

Preprint

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Background: We have identified molecules that exhibit synthetic lethality in cells with loss of the neurofibromin 1 (NF1) tumor suppressor gene. However, recognizing tumors that have inactivation of the NF1 tumor suppressor function is challenging because the loss may occur via mechanisms that do not involve mutation of the genomic locus. Degradation of the NF1 protein, independent of NF1 mutation status, phenocopies inactivating mutations to drive tumors in human glioma cell lines. NF1 inactivation may alter the transcriptional landscape of a tumor and allow a machine learning classifier to detect which tumors will benefit from synthetic lethal molecules.

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The Placental Gene PEG10 Promotes Progression of Neuroendocrine Prostate Cancer

Cited by 239 publications

References 51 publications

The Role of Epigenetics and Long Noncoding RNA MIAT in Neuroendocrine Prostate Cancer

The Role of Epigenetics and Long Noncoding RNA MIAT in Neuroendocrine Prostate Cancer

PEG10 promotes human breast cancer cell proliferation, migration and invasion

A machine learning classifier trained on cancer transcriptomes detects NF1 inactivation signal in glioblastoma

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