An integrated functional and clinical genomics approach reveals genes driving aggressive metastatic prostate cancer

Das, Rajdeep; Sjöström, Martin; Shrestha, Raunak; Yogodzinski, Christopher; Egusa, Emily A.; Chesner, Lisa N.; Chen, William S.; Chou, Jonathan; Dang, Donna K.; Swinderman, Jason; Ge, Alex Y.; Hua, Junjie; Kabir, Shaheen; Quigley, David A.; Small, Eric J.; Ashworth, Alan; Feng, Felix Y.; Gilbert, Luke A.

doi:10.1038/s41467-021-24919-7

Cited by 24 publications

(13 citation statements)

References 62 publications

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“…Das et al conducted the first genome-scale CRISPRi screen in metastatic PCa models to identify genes required for cell survival [ 62 ]. They demonstrated that Kinesin Family Member 4A (KIF4A) and WD Repeat Domain 62 (WDR62) promote aggressive PCa phenotypes in vitro and in vivo, leading to nominating KIF4A and WDR62 as PCa driver genes, combined with their clinical data.…”

Section: Crispr Screens In Pcamentioning

confidence: 99%

CRISPR Screen Contributes to Novel Target Discovery in Prostate Cancer

Tsujino

Komura

Inamoto

et al. 2021

IJMS

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Prostate cancer (PCa) is one of the common malignancies in male adults. Recent advances in omics technology, especially in next-generation sequencing, have increased the opportunity to identify genes that correlate with cancer diseases, including PCa. In addition, a genetic screen based on CRISPR/Cas9 technology has elucidated the mechanisms of cancer progression and drug resistance, which in turn has enabled the discovery of new targets as potential genes for new therapeutic targets. In the era of precision medicine, such knowledge is crucial for clinicians in their decision-making regarding patient treatment. In this review, we focus on how CRISPR screen for PCa performed to date has contributed to the identification of biologically critical and clinically relevant target genes.

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Section: Crispr Screens In Pcamentioning

confidence: 99%

CRISPR Screen Contributes to Novel Target Discovery in Prostate Cancer

Tsujino

Komura

Inamoto

et al. 2021

IJMS

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“…We identified a novel circRNA, termed circWDR62, and confirmed that the expression of circWDR62 was significantly upregulated in exosomes derived from TMZ-resistant glioma cells and serum samples from patients with recurrent glioma. Previous evidence indicates that the expression of the host gene WDR62 is significantly upregulated in most tumours and correlates with poor prognosis in multiple cancers [ 39 , 40 ]. Subsequently, an RNase R treatment assay was carried out to confirm the stability of circWDR62.…”

Section: Discussionmentioning

confidence: 99%

Exosomal circWDR62 promotes temozolomide resistance and malignant progression through regulation of the miR-370-3p/MGMT axis in glioma

et al. 2022

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Exosome-mediated delivery of circular RNAs (circRNAs) is implicated in cancer progression. However, the role of exosomal circRNAs in the chemotherapy resistance of tumours remains poorly understood. Here we identified a novel circRNA, circWDR62. It was found that circWDR62 expression was upregulated in TMZ-resistant glioma cells and TMZ-resistant glioma cell-derived exosomes compared with their controls by using high-throughput microarray analysis and quantitative real-time polymerase chain reaction, and high circWDR62 expression was associated with poor prognosis of glioma. Functionally, downregulation of circWDR62 expression could significantly inhibit the TMZ resistance and malignant progression of glioma. Further mechanistic studies showed that circWDR62 plays a role by sponging miR-370-3p as a competing endogenous RNA. Rescue experiments confirmed that MGMT is the downstream target of the circWDR62/miR-370-3p axis in glioma. In addition, circWDR62 could be transported between TMZ-resistant and TMZ-sensitive glioma cells via exosomes. Exosomal circWDR62 from TMZ-resistant cells conferred TMZ resistance in recipient sensitive cells while also enhancing the proliferation, migration and invasion of these cells. A series of clinical and in vivo trials corroborated that exosomal circWDR62 could promote TMZ chemoresistance and malignant progression of glioma. Our results demonstrate for the first time that exosome-mediated delivery of circWDR62 can promote TMZ resistance and malignant progression via targeting of the miR-370-3p/MGMT axis in vitro and in vivo in glioma, providing a new therapeutic strategy. Moreover, exosomal circWDR62 in human serum may serve as a promising therapeutic target and prognostic marker for glioma therapy.

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“…Recent studies show that PLK1 and KIF4A as biomarkers have a high prognosis value in patients with prostate cancer ( Gao et al, 2018 ; Cao et al, 2020 ; Liu et al, 2020 ; Wu et al, 2020 ; Das et al, 2021 ). PLK1 has been proven to be a potent and promising target for prostate cancer treatment ( Mao et al, 2018 ; Shin et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

A Novel Gene Signature Associated With “E2F Target” Pathway for Predicting the Prognosis of Prostate Cancer

Xia

Wang

et al. 2022

Front. Mol. Biosci.

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Background: The effect of the adenoviral early region 2 binding factors (E2Fs) target pathway on prostate cancer is not clear. It is necessary to establish an E2F target-related gene signature to predict prognosis and facilitate clinical decision-making.Methods: An E2F target-related gene signature was established by univariate and LASSO Cox regression analyses, and its predictive ability was verified in multiple cohorts. Moreover, the enrichment pathway, immune microenvironment, and drug sensitivity of the activated E2F target pathway were also explored.Results: The E2F target-related gene signature consisted of MXD3, PLK1, EPHA10, and KIF4A. The patients with high-risk scores showed poor prognosis, therapeutic resistance, and immunosuppression, along with abnormal growth characteristics of cells. Tinib drugs showed high sensitivity to the expression of MXD3 and EPHA10 genes.Conclusion: Our research established an E2F target-related signature for predicting the prognosis of prostate cancer. This study provides insights into formulating individualized detection and treatment as well as provides a theoretical basis for future research.

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An integrated functional and clinical genomics approach reveals genes driving aggressive metastatic prostate cancer

Cited by 24 publications

References 62 publications

CRISPR Screen Contributes to Novel Target Discovery in Prostate Cancer

CRISPR Screen Contributes to Novel Target Discovery in Prostate Cancer

Exosomal circWDR62 promotes temozolomide resistance and malignant progression through regulation of the miR-370-3p/MGMT axis in glioma

A Novel Gene Signature Associated With “E2F Target” Pathway for Predicting the Prognosis of Prostate Cancer

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