Review
Biochemistry & Molecular Biology
Demitria M. Vasilatis, Christopher A. Lucchesi, Paramita M. Ghosh
Summary: Dogs naturally develop prostate cancer similar to aggressive forms found in humans. Prostate cancer samples in dogs often lack androgen receptor (AR), which can enhance our understanding of AR-indifferent prostate cancer in humans. This review highlights the molecular similarities between dog and human prostate cancer variants, suggesting the potential use of dogs as pre-clinical animal models for developing new therapies and diagnostics that can benefit both species.
Article
Chemistry, Multidisciplinary
Joslyn Quick, Nancy Dos Santos, Miffy H. Y. Cheng, Nisha Chander, Cedric A. Brimacombe, Jayesh Kulkarni, Roy van der Meel, Yuen Yi C. Tam, Dominik Witzigmann, Pieter R. Cullis
Summary: This study explores the use of RNA interference to target a universally conserved region of all androgen receptor splice variants for cleavage and degradation, thereby eliminating protein level resistance mechanisms. Through testing five siRNA sequences designed against exon 1 of the AR mRNA, it was found that some induced potent knockdown of full-length and truncated variant ARs in the 22Rv1 human prostate cancer cell line.
JOURNAL OF CONTROLLED RELEASE
(2022)
Editorial Material
Cell Biology
Li Xin
Summary: EZH2 has been shown to promote the development of castration-resistant prostate cancer (CRPC) by interacting with the androgen receptor (AR) to reprogram its transcriptional activity, facilitating the transition of CRPC into a lineage infidelity state.
NATURE CELL BIOLOGY
(2021)
Article
Cell Biology
Marco Del Giudice, John G. Foster, Serena Peirone, Alberto Rissone, Livia Caizzi, Federica Gaudino, Caterina Parlato, Francesca Anselmi, Rebecca Arkell, Simonetta Guarrera, Salvatore Oliviero, Giuseppe Basso, Prabhakar Rajan, Matteo Cereda
Summary: FOXA1 plays a key role in dysregulation of alternative splicing in prostate cancer by controlling transcription factor expression and binding to splicing-related genes, leading to the production of dominant isoforms and influencing patient survival.
Article
Biochemistry & Molecular Biology
Khrystany T. Isebia, Martijn P. Lolkema, Guido Jenster, Ronald de Wit, John W. M. Martens, Job van Riet
Summary: This study found that in metastatic castration-resistant prostate cancer, in addition to AR-V7, AR45 and AR-V3 were also commonly seen AR splice variants. The presence of any AR-Vs may be associated with higher AR expression. These AR-Vs could potentially serve as predictive and prognostic biomarkers in metastatic castration-resistant prostate cancer, similar or complementary to AR-V7.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Tuyen Thanh Tran, Keesook Lee
Summary: TR3 overexpression alters AR expression, splicing process, and activity, increasing the androgen independence of AR signaling in advanced prostate cancer. TR3 also enhances cell proliferation, mobility, and tumorigenesis of AR-positive and androgen-independent prostate cancer cells.
Article
Oncology
Zhengfang Liu, Cheng Liu, Keqiang Yan, Jikai Liu, Zhiqing Fang, Yidong Fan
Summary: The huaier extract demonstrated potent antiproliferative effects in both hormone sensitive prostate cancer (HSPC) and castration-resistant prostate cancer (CRPC) cells by downregulating AR-FL and AR-V7 mRNA levels via targeting the SMYD3 signaling pathway, and enhancing proteasome-mediated protein degradation of AR-FL and AR-V7 by downregulating USP14. Additionally, the extract inhibited AR transcriptional activity and their nuclear translocation, and could re-sensitize enzalutamide-resistant prostate cancer cells to enzalutamide treatment in vitro and in vivo models.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Haozhe Zhang, Yi Zhou, Zengzhen Xing, Rajiv Kumar Sah, Junqi Hu, Hailiang Hu
Summary: This review discusses the close relationship between the evolution of prostate cancer and androgen levels and the status of the androgen receptor. It also explores how alterations in androgen metabolism contribute to the resistance to anti-androgen therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Andrology
Sean Seltzer, Paresa N. Giannopoulos, Tarek A. Bismar, Mark Trifiro, Miltiadis Paliouras
Summary: A proteomics study identified various protein interactors with tumorigenic annotations, including RNA splicing factors, in prostate cancer cells. The study further investigated the functional role of AR-mediated alternative RNA splicing in PCa disease progression using two AR-interacting RNA splicing factors.
ASIAN JOURNAL OF ANDROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Margherita Corti, Stefano Lorenzetti, Alessandro Ubaldi, Romano Zilli, Daniele Marcoccia
Summary: The role of endocrine disruptors in the human prostate gland is overlooked, but they can influence the homeostasis and diseases of the prostate, including prostate cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Neele Wuestmann, Konstantin Seitzer, Verena Humberg, Julia Vieler, Norbert Grundmann, Julie Steinestel, Dorothee Tiedje, Stefan Duensing, Laura-Maria Krabbe, Martin Boegemann, Andres Jan Schrader, Christof Bernemann, Katrin Schlack
Summary: This study found that the level of AR-FL and the appearance and increase of AR-Vs are associated with elevated levels of AR pre-mRNA in prostate cancer cells. The levels of AR-FL and AR-Vs also increase during disease progression. In patients undergoing ARTA treatment, AR-FL shows prognostic value but not predictive value. Additionally, even AR-V positive patients show a significant clinical response to ARTA treatment. Therefore, AR-FL and AR-V may be considered as prognostic biomarkers in mCRPC patients, but not predictive biomarkers.
BIOMARKER RESEARCH
(2023)
Review
Endocrinology & Metabolism
Florian Le Billan, Gloria Umogbai, Carolyn L. Cummins
Summary: Steroid hormones not only regulate gene transcription but also modulate the alternative splicing of pre-mRNA, acting through binding to nuclear receptors. The effect of steroid hormones on alternative splicing is time-, gene-, and tissue-specific. Mechanisms by which steroid hormones regulate alternative splicing include the recruitment of dual-function proteins, transcriptional regulation of splicing factor levels, alternative splicing of splicing factors or transcription factors, and regulation of elongation rate.
Review
Biochemistry & Molecular Biology
Tae Jin Kim, Young Hwa Lee, Kyo Chul Koo
Summary: The androgen receptor (AR) plays a crucial role in the development and progression of prostate cancer (PCa), and treatment for hormone-sensitive prostate cancer (HSPC) relies heavily on androgen deprivation therapy (ADT). Despite most patients progressing to castration-resistant prostate cancer (CRPC), studies suggest that manipulating alternative molecular pathways can help improve current treatments and develop novel therapies for CRPC management.
Article
Biochemistry & Molecular Biology
Wei Liu, Chunyu Wang, Shengli Wang, Kai Zeng, Shan Wei, Ning Sun, Ge Sun, Manlin Wang, Renlong Zou, Wensu Liu, Lin Lin, Huijuan Song, Zining Jin, Yue Zhao
Summary: PRPF6 plays a key role in enhancing the actions of AR full length and variant 7 in prostate cancer, promoting AR-induced transactivation and tumor growth, as well as being highly expressed in human prostate cancer samples.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Oncology
Yuri Tolkach, Anika Kremer, Gabor Lotz, Matthias Schmid, Thomas Mayr, Sarah Foerster, Stephan Garbe, Sana Hosni, Marcus Cronauer, Ildiko Kocsmar, Eva Kocsmar, Peter Riesz, Abdullah Alajati, Manuel Ritter, Joerg Ellinger, Carsten-Henning Ohlmann, Glen Kristiansen
Summary: The expression of androgen receptor splice variants, particularly AR-V7, in prostate cancer patients undergoing androgen deprivation therapy (ADT) may contribute to reduced therapy effects in patients receiving additional PARP inhibition due to the modulation of DNA repair gene expression. These findings suggest that AR splice variants could be further studied as predictive biomarkers for therapy response in this setting.