LncRNA PCBP1-AS1-mediated AR/AR-V7 deubiquitination enhances prostate cancer enzalutamide resistance

Zhang, Boya; Zhang, Mingpeng; Shen, Chunyi; Liu, Guancong; Zhang, Fan; Hou, Jingyu; Yao, Weitao

doi:10.1038/s41419-021-04144-2

Cited by 31 publications

(23 citation statements)

References 37 publications

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“…Due to clinical importance and association with biological processes in many malignancies, LINC01116 could be a crucial biomarker for the prediction and therapeutic interventions of malignant tumors ( 64 ). PCBP1-AS1 could facilitate the AR/AR-V7 deubiquitination, resulting in the protection of AR/AR-V7 against degeneration ( 65 ). In vitro and in vivo studies have shown that targeting PCBP1-AS1 may improve the therapeutic responsiveness of enzalutamide-resistant cancers and suppress the metastasis of LUAD ( 65 , 66 ).…”

Section: Discussionmentioning

confidence: 99%

“…PCBP1-AS1 could facilitate the AR/AR-V7 deubiquitination, resulting in the protection of AR/AR-V7 against degeneration ( 65 ). In vitro and in vivo studies have shown that targeting PCBP1-AS1 may improve the therapeutic responsiveness of enzalutamide-resistant cancers and suppress the metastasis of LUAD ( 65 , 66 ). SNHG10 was shown to be overexpressed in gastric cancer (GC) cells.…”

Section: Discussionmentioning

confidence: 99%

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Development and Validation of Lactate Metabolism-Related lncRNA Signature as a Prognostic Model for Lung Adenocarcinoma

et al. 2022

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BackgroundLung cancer has been a prominent research focus in recent years due to its role in cancer-related fatalities globally, with lung adenocarcinoma (LUAD) being the most prevalent histological form. Nonetheless, no signature of lactate metabolism-related long non-coding RNAs (LMR-lncRNAs) has been developed for patients with LUAD. Accordingly, we aimed to develop a unique LMR-lncRNA signature to determine the prognosis of patients with LUAD.MethodThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to derive the lncRNA expression patterns. Identification of LMR-lncRNAs was accomplished by analyzing the co-expression patterns between lncRNAs and LMR genes. Subsequently, the association between lncRNA levels and survival outcomes was determined to develop an effective signature. In the TCGA cohort, Cox regression was enlisted to build an innovative signature consisting of three LMR-lncRNAs, which was validated in the GEO validation cohort. GSEA and immune infiltration analysis were conducted to investigate the functional annotation of the signature and the function of each type of immune cell.ResultsFourteen differentially expressed LMR-lncRNAs were strongly correlated with the prognosis of patients with LUAD and collectively formed a new LMR-lncRNA signature. The patients could be categorized into two cohorts based on their LMR-lncRNA signatures: a low-risk and high-risk group. The overall survival of patients with LUAD in the high-risk group was considerably lower than those in the low-risk group. Using Cox regression, this signature was shown to have substantial potential as an independent prognostic factor, which was further confirmed in the GEO cohort. Moreover, the signature could anticipate survival across different groups based on stage, age, and gender, among other variables. This signature also correlated with immune cell infiltration (including B cells, neutrophils, CD4+ T cells, CD8+ T cells, etc.) as well as the immune checkpoint blockade target CTLA-4.ConclusionWe developed and verified a new LMR-lncRNA signature useful for anticipating the survival of patients with LUAD. This signature could give potentially critical insight for immunotherapy interventions in patients with LUAD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Development and Validation of Lactate Metabolism-Related lncRNA Signature as a Prognostic Model for Lung Adenocarcinoma

et al. 2022

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“…Recently, the effects of PCBP1-AS1 have been studied in multiple tumors. Zhang et al found that higher expressions of PCBP1-AS1 might reveal poorer prognoses for sufferers and might reinforce the deubiquitination of AR/AR-V7 via stabilising the USP22-AR/AR-V7 complexes, hence avoiding AR/AR-V7 degradation via the ubiquitin-proteasome channel [ 33 ]. Luo and his group revealed that PCBP1-AS1 was highly expressed in human hepatocellular carcinoma and markedly related to unsatisfactory prognoses in sufferers with hepatocellular carcinoma.…”

Section: Discussionmentioning

confidence: 99%

A Two-eRNA-Based Signature Can Impact the Immune Status and Predict the Prognosis and Drug Sensitivity of Lung Adenocarcinoma

Wang

Zhou

et al. 2022

Journal of Immunology Research

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Enhancer RNAs (eRNAs) are intergenic long noncoding RNAs (lncRNAs) participating in the development of malignant cancers via targeting cancer-associated genes and immune checkpoints. Immune infiltration of the tumor microenvironment was positively associated with overall survival (OS) in lung adenocarcinoma (LUAD). In this study, we aimed to explore the clinical significance of PCBP1-AS1 in LUAD and developed a novel prognostic signature based on two eRNAs. Our team discovered that the expression of PCBP1-AS1 was distinctly downregulated in LUAD specimens compared with nontumor specimens. Lower PCBP1-AS1 expression was related to advanced clinical stages and poor prognosis. KEGG analysis unveiled that the coexpression genes of PCBP1-AS1 were involved in the regulation of several tumor-related pathways. In addition, remarkable associations were observed between the expression of PCBP1-AS1 and the levels of several immune cells. Then, we used PCBP1-AS1 and TBX5-AS1 to develop a prognostic model. Survival assays unveiled that patients with higher risk scores exhibited a shorter OS in contrast to patients with lower risk scores. In addition, multivariable Cox regressive analysis indicated that the risk score was an independent prediction factor in LUAD sufferers. The anticancer drug sensitivity analysis indicated that risk score had a positive relationship with several anticancer drugs. Taken together, our findings indicated PCBP1-AS1 as a function modulator in LUAD development. In addition, we constructed a robust immune-related eRNA signature which might be a clinical prognosis factor for LUAD patients.

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“…Previous studies reported that LncRNA LINC00675 and HOTAIR were markedly upregulated in androgen-insensitive PCa cell lines and CRPC patients, blocking the interaction of AR proteins with MDM2 and thereby preventing AR ubiquitination and protein degradation ( Zhang et al, 2015 ; Yao et al, 2020 ). LncRNA PCBP1-AS1 ( Zhang B et al, 2021 ) was reported to be able to stabilize AR via promoting the stability of USP22-AR complex by binding to AR NTD domain and enhancing AR de-ubiquitination. Importantly, targeting LINC00675, HOTAIR and PCBP1-AS1 all could effectively inhibit the growth and invasion ability of PCa cells and restore the drug sensitivity of Enzalutamide-resistant PCa cells, which offered distinct view for future clinical utilization.…”

Section: Ar Pathwaymentioning

confidence: 99%

The Role of Long Non-Coding RNAs in Epithelial-Mesenchymal Transition-Related Signaling Pathways in Prostate Cancer

Shen

Peng

Xia

et al. 2022

Front. Mol. Biosci.

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Prostate cancer (PCa) is one of the most common male malignancies with frequent remote invasion and metastasis, leading to high mortality. Epithelial-mesenchymal transition (EMT) is a fundamental process in embryonic development and plays a key role in tumor proliferation, invasion and metastasis. Numerous long non-coding RNAs (lncRNAs) could regulate the occurrence and development of EMT through various complex molecular mechanisms involving multiple signaling pathways in PCa. Given the importance of EMT and lncRNAs in the progression of tumor metastasis, we recapitulate the research progress of EMT-related signaling pathways regulated by lncRNAs in PCa, including AR signaling, STAT3 signaling, Wnt/β-catenin signaling, PTEN/PI3K/AKT signaling, TGF-β/Smad and NF-κB signaling pathways. Furthermore, we summarize four modes of how lncRNAs participate in the EMT process of PCa via regulating relevant signaling pathways.

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LncRNA PCBP1-AS1-mediated AR/AR-V7 deubiquitination enhances prostate cancer enzalutamide resistance

Cited by 31 publications

References 37 publications

Development and Validation of Lactate Metabolism-Related lncRNA Signature as a Prognostic Model for Lung Adenocarcinoma

Development and Validation of Lactate Metabolism-Related lncRNA Signature as a Prognostic Model for Lung Adenocarcinoma

A Two-eRNA-Based Signature Can Impact the Immune Status and Predict the Prognosis and Drug Sensitivity of Lung Adenocarcinoma

The Role of Long Non-Coding RNAs in Epithelial-Mesenchymal Transition-Related Signaling Pathways in Prostate Cancer

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