Dataset Information

Characterization of SPSB1-regulated proteins following CRISPR APA engineering

ABSTRACT: Proteomics analysis was performed in 22Rv1, LNCaP-abl and BPH1 cells after transfection of 3'UTRCES-SPSB1 systems

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: FURONG HUANG

LAB HEAD: Qianben Wang

PROVIDER: PXD071209 | Pride | 2026-06-29

REPOSITORIES: Pride

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Publications

Programmable mRNA 3'UTR engineering restores MHC-I and overcomes immune evasion in prostate cancer.

Huang Furong F Yuan Fuwen F Li Kexin K Cui Ya Y Li Lei L Ye Wenbin W Cui Zhifen Z Yan Jingyue J Chen Qiang Q Nicchitta Christopher C Zhang Yuebao Y Hankey William W Everitt Jeffrey J Huang Kai-Lieh KL Wang Mu-En ME Chen Ming M Huang Jiaoti J Wang Hongyan H Wagner Eric J EJ Lu Xin X Dong Yizhou Y Li Wei W Wang Qianben Q

Nature biomedical engineering 20260616

Immune-cold tumours such as prostate cancer often resist immune checkpoint therapies (ICT) due to impaired antigen presentation via major histocompatibility complex class I (MHC-I). While MHC-I downregulation is a common immune evasion mechanism, no approved therapies selectively restore MHC-I expression in tumours. We developed a programmable RNA engineering platform, termed the 3'UTR CRISPR/dCas13 Engineering System (3'UTRCES), to precisely manipulate mRNA alternative polyadenylation (APA) in ...[more]

PMID: 42303814

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Project description:The development and progression of castrate resistant prostate cancer (CRPC), a lethal disease, is thought to be driven by multiple events. A hallmark of CRPC is the ability to evade the cytotoxic effects of anti-androgen therapy. Importantly, persistent androgen receptor (AR) signalling is thought to play a principal role in maintaining CRPC. The precise molecular alterations driving this condition, however, are not clearly understood. Our previous studies identified specific metabolic alterations associated with localized prostate cancer (PCa) and CRPC, implicating metabolic re-programming in disease progression. Building on these findings, using a novel network-based integromics approach, here we show distinct alterations in the Hexosamine Biosynthetic Pathway (HBP) to be critical for sustaining the castrate resistant state. We found expression of the HBP enzyme glucosamine-phosphate N-acetyltransferase 1 (GNPNAT1) was regulated by androgens and elevated in androgen dependent (AD) PCa while relatively diminished in CRPC possessing either full length AR (AR-FL) or the spliced V7 variant (AR-V7). Genetic loss of function experiments for GNPNAT1 in CRPC-like cells led to increased proliferation and aggressiveness, both, in vitro and in vivo. This was mediated by specific cell cycle genes regulated by the PI3K-AKT pathway activating either AR in cells with AR-FL or SP1-ChREBP (carbohydrate response element binding protein) in cells containing AR-V7. Strikingly, addition of HBP metabolite UDP-N-acetylglucosamine (UDP) to CRPC-like cells reduced the expression of cell cycle genes and attenuated tumor cell proliferation, both in vitro and in vivo. Furthermore, addition of UDP sensitized CRPC-like cells, inclusive of those possessing AR-V7, to enzalutamide, demonstrating the therapeutic value of targeting altered metabolic pathways in lethal PCa. We anticipate that our findings will motivate the development of novel metabolic therapeutic strategies that complement existing treatments for men with lethal prostate cancer We used microarray analysis to determine key molecular alterations associated with inhibition of HBP pathway in CRPC by knocking down GNPNAT1 transcript level using lentiviral particle bearing shRNA in 22Rv1 and LNCaP-ABL cells GNPNAT1 expression was knockdown in two independent prostate cancer cells, 22Rv1 and LNCaP-ABL

			Action	DRS
	22Rv1_SPSB1g5_rep1.mgf	Mgf
	22Rv1_SPSB1g5_rep1.mzid	Mzid
	22Rv1_SPSB1g5_rep1.raw	Raw
	22Rv1_SPSB1g5_rep2.mgf	Mgf
	22Rv1_SPSB1g5_rep2.mzid	Mzid