Biology and Clinical Implications of the 19q13 Aggressive Prostate Cancer Susceptibility Locus

Gao, Ping; Xia, Ji‐Han; Sipeky, Csilla; Dong, Xian-Zi; Zhang, Qin; Yang, Yongfeng; Zhang, Peng; Cruz, Sara Pereira; Zhang, Kai; Zhu, Jing; Lee, Hang-Mao; Suleman, Sufyan; Giannareas, Nikolaos; Liu, Song; Tammela, Teuvo L.J.; Auvinen, Anssi; Wang, Xiaoyue; Huang, Qilai; Wang, Liguo; Manninen, Aki; Vaarala, Markku H.; Wang, Liang; Schleutker, Johanna; Wei, Gong-Hong

doi:10.1016/j.cell.2018.06.003

Cited by 128 publications

(150 citation statements)

References 54 publications

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“…While previous studies have reported the regulation of a single transcription factor at a given risk locus (Guo et al, 2016;Huang et al, 2014), here, we demonstrated that two different transcription factors can converge at a single SNP locus to regulate the expression of a lncRNA. Furthermore, while we find that NKX3.1 and YY1 preferentially bind to the non-risk alleles of rs11672691 and rs887391, an independent study reported that HOXA2 preferentially binds to the risk allele of rs11672691 (Gao et al, 2018). It is therefore possible that the synergy of multiple transcription factors binding facilitate the promoter-enhancer switching.…”

Section: Discussionmentioning

confidence: 55%

Risk SNP-Mediated Promoter-Enhancer Switching Drives Prostate Cancer through lncRNA PCAT19

Hua

Ahmed

Guo

et al. 2018

Cell

265

228

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The prostate cancer (PCa) risk-associated SNP rs11672691 is positively associated with aggressive disease at diagnosis. We showed that rs11672691 maps to the promoter of a short isoform of long noncoding RNA PCAT19 (PCAT19-short), which is in the third intron of the long isoform (PCAT19-long). The risk variant is associated with decreased and increased levels of PCAT19-short and PCAT19-long, respectively. Mechanistically, the risk SNP region is bifunctional with both promoter and enhancer activity. The risk variants of rs11672691 and its LD SNP rs887391 decrease binding of transcription factors NKX3.1 and YY1 to the promoter of PCAT19-short, resulting in weaker promoter but stronger enhancer activity that subsequently activates PCAT19-long. PCAT19-long interacts with HNRNPAB to activate a subset of cell-cycle genes associated with PCa progression, thereby promoting PCa tumor growth and metastasis. Taken together, these findings reveal a risk SNP-mediated promoter-enhancer switching mechanism underlying both initiation and progression of aggressive PCa.

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Section: Discussionmentioning

confidence: 55%

Risk SNP-Mediated Promoter-Enhancer Switching Drives Prostate Cancer through lncRNA PCAT19

Hua

Ahmed

Guo

et al. 2018

Cell

265

228

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“…AR enhancer duplication [18,33,34] and RB1 exon 7-17 tandem duplication [106] leading to AR overexpression and RB1 protein loss respectively are relevant examples of events discovered through whole genome sequencing studies. Similarly, SNPs located in noncoding inter-or intragenic regions were shown to be associated with specific subtypes of prostate cancer and with disease aggressiveness [107][108][109][110] .…”

Section: Resultsmentioning

confidence: 99%

Evolution of the prostate cancer genome towards resistance

Lorenzin¹,

Demichelis²

2019

JTGG

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The clinical behavior of prostate cancer is highly heterogeneous, with most patients diagnosed with localized disease that successfully responds to surgery or radiotherapy or that can be followed by active surveillance. However, a fraction of men will relapse after initial treatment and eventually progress to an aggressive resistant form with metastasis spreading and high mortality, a state referred to as castration resistant prostate cancer (CRPC). The technological advances in next generation sequencing have enabled the deep genomic and epigenomic characterization of both the hormone naïve and CRPC states, leading to the definition of molecular subclasses of prostate cancer that could inform the clinicians on therapeutic strategies. These studies also shed light on the mechanisms driving resistance to therapy. CRPCs adapt to androgen receptor (AR) signaling impairment-which follows first-line therapies as androgen deprivation or AR targeting-by restoring the nuclear receptor signaling by means of multiple mechanisms. Alternatively, tumor cells might become resistant to targeted therapies by exploiting lineage plasticity and activating alternative pathways. This review will discuss the main mechanisms leading to the emergence of resistance to therapy in prostate cancer patients in the context of genomic and molecular features of CRPC and on their causal role in the development of resistance.

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“…Taken together, these data provide evidence for functional contribution of rs2680700 in changing linc0597 expression or stability. However, the exact roles of these two SNPs in RA still need further exploration [45,46]. Additionally, we attempted to discover the correlations of H19 expression with their gene polymorphisms in RA patients, but still no statistically significant results were found.…”

Section: Discussionmentioning

confidence: 99%

Decreased H19, GAS5, and linc0597 Expression and Association Analysis of Related Gene Polymorphisms in Rheumatoid Arthritis

Zhang

Zhao

et al. 2019

Biomolecules

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Long noncoding RNAs (lncRNAs) widely participate in human diseases by regulating gene transcription, modulating protein function, or acting as ceRNAs. Yet, their roles in rheumatoid arthritis (RA) remain obscure. In this study, the expression of three lncRNAs (H19, GAS5, and linc0597) in peripheral blood mononuclear cells (PBMCs) were detected in 77 RA patients and 78 controls using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The association of lncRNAs related gene polymorphisms with RA were evaluated in 828 RA patients and 780 controls using TaqMan single nucleotide polymorphism (SNP) genotyping assays. We observed that the expression levels of H19, GAS5 and linc0597 were down-regulated in PBMCs of RA patients, of which GAS5 level decreased in patients with hypocomplementemia, and negatively correlated with C-reactive protein (CRP) level in RA patients. Moreover, we highlighted two related potential functional SNPs, GAS5 rs6790 and linc0597 rs2680700 for associations with RA susceptibility. The precise roles of these lncRNAs in mechanism of RA remain to be further explored.

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Biology and Clinical Implications of the 19q13 Aggressive Prostate Cancer Susceptibility Locus

Cited by 128 publications

References 54 publications

Risk SNP-Mediated Promoter-Enhancer Switching Drives Prostate Cancer through lncRNA PCAT19

Risk SNP-Mediated Promoter-Enhancer Switching Drives Prostate Cancer through lncRNA PCAT19

Evolution of the prostate cancer genome towards resistance

Decreased H19, GAS5, and linc0597 Expression and Association Analysis of Related Gene Polymorphisms in Rheumatoid Arthritis

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