Identification of AR-V7 downstream genes commonly targeted by AR/AR-V7 and specifically targeted by AR-V7 in castration resistant prostate cancer

Sugiura, Masahiro; Sato, Hiroaki; Okabe, Atsushi; Fukuyo, Masaki; Mano, Yasunobu; Shinohara, Ken ichi; Rahmutulla, Bahityar; Higuchi, Kosuke; Maimaiti, Maihulan; Kanesaka, Manato; Imamura, Yusuke; Furihata, Tomomi; Sakamoto, Shinichi; Komiya, Akira; Anzai, Naohiko; Kanai, Yoshikatsu; Luo, Jun; Ichikawa, Tomohiko; Kaneda, Atsushi

doi:10.1016/j.tranon.2020.100915

Cited by 33 publications

(42 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The studies seeking to elucidate variant action have yielded conflicting results. There is good agreement that AR-V7 and other variants can regulate many of the same genes, but there is a substantial debate about whether AR-V7 and other variants also regulate a substantial set of unique targets or have minimal or no unique activities [16][17][18][19][20]25,26,39 . Similarly, some investigators have identified unique AR-V7 chromatin binding sites, while others have described these as artifacts/unreliable 16,17,19,40 .…”

Section: Discussionmentioning

confidence: 99%

Cistrome and transcriptome analysis identifies unique androgen receptor (AR) and AR- V7 splice variant chromatin binding and transcriptional activities

Basil

Robertson

Bingman

et al. 2021

Preprint

View full text Add to dashboard Cite

The constitutively active androgen receptor (AR) splice variant, AR-V7, plays an important role in resistance to androgen deprivation therapy in castration resistant prostate cancer (CRPC). Studies seeking to determine whether AR-V7 is a partial mimic of the AR, or also has unique activities, and whether the AR-V7 cistrome contains unique binding sites have yielded conflicting results. One limitation in many studies has been the low level of AR variant compared to AR. Here, LNCaP and VCaP cell lines in which AR-V7 expression can be induced to match the level of AR, were used to compare the activities of AR and AR-V7. The two AR isoforms shared many targets, but overall had distinct transcriptomes. Optimal induction of novel targets sometimes required more receptor isoform than classical targets such as PSA. The isoforms displayed remarkably different cistromes with numerous differential binding sites. Some of the unique AR-V7 sites were located proximal to the transcription start sites (TSS). A de novo binding motif similar to a half ARE was identified in many AR-V7 preferential sites and, in contrast to conventional half ARE sites that bind AR-V7, FOXA1 was not enriched at these sites. This supports the concept that the AR isoforms have unique actions with the potential to serve as biomarkers or novel therapeutic targets.

show abstract

Section: Discussionmentioning

confidence: 99%

Cistrome and transcriptome analysis identifies unique androgen receptor (AR) and AR- V7 splice variant chromatin binding and transcriptional activities

Basil

Robertson

Bingman

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, we recently identified 4F2hc as one of the main target genes for AR-V7. Upregulation of 4F2hc through AR-V7 contributes to the progression of CRPC 23 .…”

Section: Introductionmentioning

confidence: 99%

The heavy chain of 4F2 antigen promote prostate cancer progression via SKP-2

Maimaiti

Sakamoto

Sugiura

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

The 4F2 cell-surface antigen heavy chain (4F2hc) forms a heterodimeric complex with L-type amino acid transporter 1 (LAT1) and transports large neutral essential amino acids. However, in contrast to the traditional role of LAT1 in various cancers, the role of 4F2hc has largely remained unknown. The role of 4F2hc in prostate cancer was studied. Treatment of C4-2 cells with si4F2hc was found to suppress cellular growth, migratory and invasive abilities, with this effect occurring through the cell cycle, with a significant decrease in S phase and a significant increase in G0/G1 phase, suggesting cell cycle arrest. In addition, it was proven by RNA seq that the key to 4F2hc’s impact on cancer is SKP2. si4F2hc upregulates the protein expression of cyclin-dependent kinase inhibitors (P21cip1, P27kip1) through the downstream target SKP2. Furthermore, the expression of 4F2hc and LAT1 in prostate cancer cells suggests the importance of 4F2hc. Multivariate analysis showed that high 4F2hc expression was an independent prognostic factor for progression-free survival (HR 11.54, p = 0.0357). High 4F2hc was related to the clinical tumour stage (p = 0.0255) and Gleason score (p = 0.0035). Collectively, 4F2hc contributed significantly to prostate cancer (PC) progression. 4F2hc may be a novel marker and therapeutic target in PC.

show abstract

“…Upregulation of 4F2hc through AR-V7 contributes to the progression of CRPC. 23 Based on the above-described ndings, it may be reasonable to expect that 4F2hc is a promising prognostic biomarker, as well as a molecular target, in PC. In this study, the oncogenic function of 4F2hc in PC and its relationship with the clinical outcome of PC patients was studied.…”

Section: Introductionmentioning

confidence: 93%

Characterization of The Expression of The Heavy Chain of 4F2 Antigen As a Therapeutic Target in Prostate Cancer

Maimaiti¹,

Sakamoto²,

Sugiura³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

The 4F2 cell-surface antigen heavy chain (4F2hc) forms a heterodimeric complex with L-type amino acid transporter 1 (LAT1) and transports large neutral essential amino acids. However, in contrast to the traditional role of LAT1 in various cancers, the role of 4F2hc has largely remained unknown. The role of 4F2hc in prostate cancer was studied. Treatment of C4-2 cells with si4F2hc was found suppress cellular growth and migratory and invasive abilities, with this effect occurring through the cell cycle, with a significant decrease in S phase and a significant increase in G0/G1 phase, suggesting cell cycle arrest. In addition, it was proven by RNA seq that the key to 4F2hc’s impact on cancer is SKP2. The expression of 4F2hc and LAT1 in prostate cancer cells suggests the importance of 4F2hc. Furthermore, si4F2hc, through the downstream target SKP2, upregulates the protein expression of cyclin-dependent kinase inhibitors (P21cip1, P27kip1). Multivariate analysis showed that high 4F2hc expression was an independent prognostic factor for progression-free survival (HR 11.54, p=0.0357). High 4F2hc was related to the clinical tumour stage (p=0.0255) and Gleason score (p=0.0035). Collectively, 4F2hc contributed significantly to prostate cancer (PC) progression. 4F2hc may be a novel marker and therapeutic target in PC.

show abstract

Identification of AR-V7 downstream genes commonly targeted by AR/AR-V7 and specifically targeted by AR-V7 in castration resistant prostate cancer

Cited by 33 publications

References 42 publications

Cistrome and transcriptome analysis identifies unique androgen receptor (AR) and AR- V7 splice variant chromatin binding and transcriptional activities

Cistrome and transcriptome analysis identifies unique androgen receptor (AR) and AR- V7 splice variant chromatin binding and transcriptional activities

The heavy chain of 4F2 antigen promote prostate cancer progression via SKP-2

Characterization of The Expression of The Heavy Chain of 4F2 Antigen As a Therapeutic Target in Prostate Cancer

Contact Info

Product

Resources

About