Clinical data investigation identifies MARK3 as an oncogenic driver in castration-resistant prostate cancer
Castration-resistant prostate cancer (CRPC) represents an aggressive and fatal form of prostate cancer that emerges following resistance to androgen deprivation therapy. Despite the availability of various drugs that can enhance the quality and prolong the survival of CRPC patients, resistance to th...
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Elsevier
2025-06-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580825000901 |
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| author | Rajnikant Raut Devesh Srivastava Vinayak Nayak Taruna Saini Parth Gupta Amit Kumar Chakraborty Chumki Choudhury Manish V. Bais Parul Mishra Ashish Misra |
| author_facet | Rajnikant Raut Devesh Srivastava Vinayak Nayak Taruna Saini Parth Gupta Amit Kumar Chakraborty Chumki Choudhury Manish V. Bais Parul Mishra Ashish Misra |
| author_sort | Rajnikant Raut |
| collection | DOAJ |
| description | Castration-resistant prostate cancer (CRPC) represents an aggressive and fatal form of prostate cancer that emerges following resistance to androgen deprivation therapy. Despite the availability of various drugs that can enhance the quality and prolong the survival of CRPC patients, resistance to these therapies is frequently observed, making the disease increasingly difficult to treat. Altered expression of kinases and phosphatases is a critical driver of CRPC and presents a potential target for more effective treatments. In this study, we have performed comprehensive transcriptomic analysis of ∼359 normal and CRPC patient samples from The Cancer Genome Atlas to identify the differentially expressed kinases and phosphatases in patient samples. We shortlisted the candidate genes based on their differential expression profiles, associations with patient survival, Gleason scores, and their impact on the fitness of prostate cancer cell lines. Our in-silico analysis identified microtubule affinity-regulating kinase 3 (MARK3) as a novel CRPC driver that is upregulated in CRPC patients, linked with poor survival outcomes, and affects the fitness of CRPC cells. Furthermore, we found that pharmacological inhibition of MARK3 using PCC0208017, a MARK3 inhibitor, leads to reduced cell viability, migration potential, and cell cycle arrest in the G1 phase in prostate cancer cells. Additionally, RNA sequencing analysis in 22Rv1 cells treated with the MARK3 inhibitor revealed that MARK3 influences genes involved in androgen response, epithelial-mesenchymal transition, mTOR, and myc-signalling, underscoring its pivotal role in CRPC progression. Taken together, our results establish MARK3 as a novel and promising therapeutic target in CRPC. |
| format | Article |
| id | doaj-art-81ad48d7ed7a40288375dd984717f5e1 |
| institution | OA Journals |
| issn | 2405-5808 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj-art-81ad48d7ed7a40288375dd984717f5e12025-08-20T02:01:05ZengElsevierBiochemistry and Biophysics Reports2405-58082025-06-014210200310.1016/j.bbrep.2025.102003Clinical data investigation identifies MARK3 as an oncogenic driver in castration-resistant prostate cancerRajnikant Raut0Devesh Srivastava1Vinayak Nayak2Taruna Saini3Parth Gupta4Amit Kumar Chakraborty5Chumki Choudhury6Manish V. Bais7Parul Mishra8Ashish Misra9Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, 502285, IndiaDepartment of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, 502285, IndiaDepartment of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, 502285, IndiaDepartment of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, 502285, IndiaDepartment of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, 502285, IndiaDepartment of Translational Dental Medicine, Boston University Henry M. Goldman School of Dental Medicine, 700 Albany Street, Boston, MA, 02118, USADepartment of Translational Dental Medicine, Boston University Henry M. Goldman School of Dental Medicine, 700 Albany Street, Boston, MA, 02118, USADepartment of Translational Dental Medicine, Boston University Henry M. Goldman School of Dental Medicine, 700 Albany Street, Boston, MA, 02118, USADepartment of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, 500046, IndiaDepartment of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, 502285, India; Corresponding author.Castration-resistant prostate cancer (CRPC) represents an aggressive and fatal form of prostate cancer that emerges following resistance to androgen deprivation therapy. Despite the availability of various drugs that can enhance the quality and prolong the survival of CRPC patients, resistance to these therapies is frequently observed, making the disease increasingly difficult to treat. Altered expression of kinases and phosphatases is a critical driver of CRPC and presents a potential target for more effective treatments. In this study, we have performed comprehensive transcriptomic analysis of ∼359 normal and CRPC patient samples from The Cancer Genome Atlas to identify the differentially expressed kinases and phosphatases in patient samples. We shortlisted the candidate genes based on their differential expression profiles, associations with patient survival, Gleason scores, and their impact on the fitness of prostate cancer cell lines. Our in-silico analysis identified microtubule affinity-regulating kinase 3 (MARK3) as a novel CRPC driver that is upregulated in CRPC patients, linked with poor survival outcomes, and affects the fitness of CRPC cells. Furthermore, we found that pharmacological inhibition of MARK3 using PCC0208017, a MARK3 inhibitor, leads to reduced cell viability, migration potential, and cell cycle arrest in the G1 phase in prostate cancer cells. Additionally, RNA sequencing analysis in 22Rv1 cells treated with the MARK3 inhibitor revealed that MARK3 influences genes involved in androgen response, epithelial-mesenchymal transition, mTOR, and myc-signalling, underscoring its pivotal role in CRPC progression. Taken together, our results establish MARK3 as a novel and promising therapeutic target in CRPC.http://www.sciencedirect.com/science/article/pii/S2405580825000901CancerCRPCProstate cancerPCC020801722Rv1MARK3 |
| spellingShingle | Rajnikant Raut Devesh Srivastava Vinayak Nayak Taruna Saini Parth Gupta Amit Kumar Chakraborty Chumki Choudhury Manish V. Bais Parul Mishra Ashish Misra Clinical data investigation identifies MARK3 as an oncogenic driver in castration-resistant prostate cancer Biochemistry and Biophysics Reports Cancer CRPC Prostate cancer PCC0208017 22Rv1 MARK3 |
| title | Clinical data investigation identifies MARK3 as an oncogenic driver in castration-resistant prostate cancer |
| title_full | Clinical data investigation identifies MARK3 as an oncogenic driver in castration-resistant prostate cancer |
| title_fullStr | Clinical data investigation identifies MARK3 as an oncogenic driver in castration-resistant prostate cancer |
| title_full_unstemmed | Clinical data investigation identifies MARK3 as an oncogenic driver in castration-resistant prostate cancer |
| title_short | Clinical data investigation identifies MARK3 as an oncogenic driver in castration-resistant prostate cancer |
| title_sort | clinical data investigation identifies mark3 as an oncogenic driver in castration resistant prostate cancer |
| topic | Cancer CRPC Prostate cancer PCC0208017 22Rv1 MARK3 |
| url | http://www.sciencedirect.com/science/article/pii/S2405580825000901 |
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