Post-transcriptional Gene Regulation by MicroRNA-194 Promotes Neuroendocrine Transdifferentiation in Prostate Cancer

Fernandes, Rayzel C.; Toubia, John; Townley, Scott L.; Hanson, Adrienne R.; Dredge, B Kate; Pillman, Katherine A.; Bert, Andrew G.; Winter, Jean M.; Iggo, Richard; Das, Rajdeep; Obinata, Daisuke; investigators, Mural; Sandhu, Shahneen; Risbridger, Gail P.; Taylor, Renea A.; Lawrence, Mitchell G.; Butler, Lisa M.; Zoubeidi, Amina; Gregory, Philip A.; Tilley, Wayne D.; Hickey, Theresa E.; Goodall, Gregory J.; Selth, Luke A.

doi:10.1016/j.celrep.2020.108585

Cited by 38 publications

(37 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The relevance of these findings was confirmed by validation in available patient cohorts and functional in vitro experiments [194]. An alternative approach exploiting Ago-HITS-CLIP based identification of miRNA binding sites revealed a correlation between miR-194 and the NE phenotype, with subsequent validation in patient samples and in vitro models [190]. On the other hand, the miR-106b~25 cluster and let-7 were implicated in regulatory mechanisms associated with NED induction, and their expression correlates with clinical observations [128,260].…”

Section: Mirnas Associated With Neuroendocrine Prostate Cancermentioning

confidence: 78%

“…The following subchapters summarize the implication of miRNAs in the NED phenotype, which were described in distinct contexts with different degrees of physiological relevance (Figure 2). [189] in clinical NEPC [190] ---• sion [244]   proliferation [245] hsa-miR-19b   in NEPC tissues [194] - MYCN [248]  PTEN…”

Section: Mirnas In the Regulation Of Ned And Prostate Cancer Progressionmentioning

confidence: 99%

“…patients [199]   in expression concomitantly   proliferation and EMT [259] --expression in primary tumour: poor prognosis [192] • serum: BCR prediction [192] • prostate biopsy: relapse prediction [193] • induces NED through FOXA1 [190] hsa-miR-375…”

Section: Mirnas In the Regulation Of Ned And Prostate Cancer Progressionmentioning

confidence: 99%

See 2 more Smart Citations

Regulation of Neuroendocrine-like Differentiation in Prostate Cancer by Non-Coding RNAs

Slabáková

Kahounová

Procházková

et al. 2021

ncRNA

View full text Add to dashboard Cite

Neuroendocrine prostate cancer (NEPC) represents a variant of prostate cancer that occurs in response to treatment resistance or, to a much lesser extent, de novo. Unravelling the molecular mechanisms behind transdifferentiation of cancer cells to neuroendocrine-like cancer cells is essential for development of new treatment opportunities. This review focuses on summarizing the role of small molecules, predominantly microRNAs, in this phenomenon. A published literature search was performed to identify microRNAs, which are reported and experimentally validated to modulate neuroendocrine markers and/or regulators and to affect the complex neuroendocrine phenotype. Next, available patients’ expression datasets were surveyed to identify deregulated microRNAs, and their effect on NEPC and prostate cancer progression is summarized. Finally, possibilities of miRNA detection and quantification in body fluids of prostate cancer patients and their possible use as liquid biopsy in prostate cancer monitoring are discussed. All the addressed clinical and experimental contexts point to an association of NEPC with upregulation of miR-375 and downregulation of miR-34a and miR-19b-3p. Together, this review provides an overview of different roles of non-coding RNAs in the emergence of neuroendocrine prostate cancer.

show abstract

Section: Mirnas Associated With Neuroendocrine Prostate Cancermentioning

confidence: 78%

Section: Mirnas In the Regulation Of Ned And Prostate Cancer Progressionmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of Neuroendocrine-like Differentiation in Prostate Cancer by Non-Coding RNAs

Slabáková

Kahounová

Procházková

et al. 2021

ncRNA

View full text Add to dashboard Cite

show abstract

“… 18 – 22 The corresponding organoids consistently maintain histological, transcriptional, and genomic features of the parental PDXs. 17 , 19 , 22 , 23 This is important because organoids and PDXs are complementary models with distinct advantages and disadvantages for preclinical testing. 11 , 24 …”

Section: Introductionmentioning

confidence: 99%

High-Throughput Imaging Assay for Drug Screening of 3D Prostate Cancer Organoids

et al. 2021

Self Cite

View full text Add to dashboard Cite

New treatments are required for advanced prostate cancer; however, there are fewer preclinical models of prostate cancer than other common tumor types to test candidate therapeutics. One opportunity to increase the scope of preclinical studies is to grow tissue from patient-derived xenografts (PDXs) as organoid cultures. Here we report a scalable pipeline for automated seeding, treatment and an analysis of the drug responses of prostate cancer organoids. We established organoid cultures from 5 PDXs with diverse phenotypes of prostate cancer, including castrate-sensitive and castrate-resistant disease, as well as adenocarcinoma and neuroendocrine pathology. We robotically embedded organoids in Matrigel in 384-well plates and monitored growth via brightfield microscopy before treatment with poly ADP-ribose polymerase inhibitors or a compound library. Independent readouts including metabolic activity and live-cell imaging–based features provided robust measures of organoid growth and complementary ways of assessing drug efficacy. Single organoid analyses enabled in-depth assessment of morphological differences between patients and within organoid populations and revealed that larger organoids had more striking changes in morphology and composition after drug treatment. By increasing the scale and scope of organoid experiments, this automated assay complements other patient-derived models and will expedite preclinical testing of new treatments for prostate cancer.

show abstract

“…The availability of characterised, transportable organoids will expand the use of these pre-clinical models. 22 of the 24 PDXs tested in this regard showed growth as organoids, to differing extents (some limited), and cryopreserved organoid cultures have been sent to other labs who have produced organoids from them 11 . This ability to grow as organoids is a feature of 14 of the 17 research-ready PDXs.…”

mentioning

confidence: 99%

Breaking down walls in prostate cancer with the MURAL collection of patient-derived xenografts

Bevan

2021

Nat Commun

View full text Add to dashboard Cite

show abstract

Post-transcriptional Gene Regulation by MicroRNA-194 Promotes Neuroendocrine Transdifferentiation in Prostate Cancer

Cited by 38 publications

References 103 publications

Regulation of Neuroendocrine-like Differentiation in Prostate Cancer by Non-Coding RNAs

Regulation of Neuroendocrine-like Differentiation in Prostate Cancer by Non-Coding RNAs

High-Throughput Imaging Assay for Drug Screening of 3D Prostate Cancer Organoids

Breaking down walls in prostate cancer with the MURAL collection of patient-derived xenografts

Contact Info

Product

Resources

About