JMJD2A participates in cytoskeletal remodeling to regulate castration-resistant prostate cancer docetaxel resistance.

Humans Male Apoptosis / genetics Cell Line, Tumor Cell Proliferation / genetics Docetaxel / pharmacology Gene Expression Regulation, Neoplastic MicroRNAs / genetics Prostatic Neoplasms, Castration-Resistant / drug therapy Tubulin / genetics Jumonji Domain-Containing Histone Demethylases / metabolism
Castration-resistant prostate cancer Docetaxel resistance JMJD2A PDX animal model miR-34a/STMN1/β3-Tubulin

Journal

BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800

Informations de publication

Date de publication:
10 May 2023
Historique:
received: 04 01 2023
accepted: 03 05 2023
medline: 12 5 2023
pubmed: 11 5 2023
entrez: 10 5 2023
Statut: epublish

Résumé

To investigate underlying mechanism of JMJD2A in regulating cytoskeleton remodeling in castration-resistant prostate cancer (CRPC) resistant to docetaxel. Tissue samples from CRPC patients were collected, and the expression of JMJD2A, miR-34a and cytoskeleton remodeling-related proteins were evaluated by qPCR, western blot and immunohistochemistry, and pathological changes were observed by H&E staining. Further, JMJD2A, STMN1 and TUBB3 were knocked down using shRNA in CRPC cell lines, and cell viability, apoptosis and western blot assays were performed. The interaction between miR-34a/STMN1/β3-Tubulin was analyzed with dual-luciferase reporter and co-immunoprecipitation assays. In clinical experiment, the CRPC-resistant group showed higher expression of JMJD2A, STMN1, α-Tubulin, β-Tubulin and F-actin, and lower expression of miR-34a and β3-Tubulin compared to the sensitive group. In vitro experiments showed that JMJD2A could regulate cytoskeletal remodeling through the miR-34a/STMN1/β3-Tubulin axis. The expression of miR-34a was elevated after knocking down JMJD2A, and miR-34a targeted STMN1. The overexpression of miR-34a was associated with a decreased expression of STMN1 and elevated expression of β3-Tubulin, which led to the disruption of the microtubule network, decreased cancer cell proliferation, cell cycle arrest in the G0/G1 phase, and increased apoptosis. JMJD2A promoted docetaxel resistance in prostate cancer cells by regulating cytoskeleton remodeling through the miR-34a/STMN1/β3-Tubulin axis.

Sections du résumé

BACKGROUND BACKGROUND
To investigate underlying mechanism of JMJD2A in regulating cytoskeleton remodeling in castration-resistant prostate cancer (CRPC) resistant to docetaxel.
METHODS METHODS
Tissue samples from CRPC patients were collected, and the expression of JMJD2A, miR-34a and cytoskeleton remodeling-related proteins were evaluated by qPCR, western blot and immunohistochemistry, and pathological changes were observed by H&E staining. Further, JMJD2A, STMN1 and TUBB3 were knocked down using shRNA in CRPC cell lines, and cell viability, apoptosis and western blot assays were performed. The interaction between miR-34a/STMN1/β3-Tubulin was analyzed with dual-luciferase reporter and co-immunoprecipitation assays.
RESULTS RESULTS
In clinical experiment, the CRPC-resistant group showed higher expression of JMJD2A, STMN1, α-Tubulin, β-Tubulin and F-actin, and lower expression of miR-34a and β3-Tubulin compared to the sensitive group. In vitro experiments showed that JMJD2A could regulate cytoskeletal remodeling through the miR-34a/STMN1/β3-Tubulin axis. The expression of miR-34a was elevated after knocking down JMJD2A, and miR-34a targeted STMN1. The overexpression of miR-34a was associated with a decreased expression of STMN1 and elevated expression of β3-Tubulin, which led to the disruption of the microtubule network, decreased cancer cell proliferation, cell cycle arrest in the G0/G1 phase, and increased apoptosis.
CONCLUSION CONCLUSIONS
JMJD2A promoted docetaxel resistance in prostate cancer cells by regulating cytoskeleton remodeling through the miR-34a/STMN1/β3-Tubulin axis.

Identifiants

DOI: 10.1186/s12885-023-10915-1 PMID: 37165308 PMC: PMC10170801
pubmed: 37165308
doi: 10.1186/s12885-023-10915-1
pii: 10.1186/s12885-023-10915-1
pmc: PMC10170801
doi:

Substances chimiques

Docetaxel 15H5577CQD
MicroRNAs 0
Tubulin 0
KDM4A protein, human EC 1.5.-
Jumonji Domain-Containing Histone Demethylases EC 1.14.11.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

423

Subventions

Organisme : Application and Basic Research Program of Sichuan Science and Technology Department
ID : 2020YJ0185
Organisme : Application and Basic Research Program of Sichuan Science and Technology Department
ID : 2022NSFSC0804
Organisme : City of Nanchong Strategic Cooperation with Local Universities Foundation of technology
ID : 18SXHZ0321
Organisme : City of Nanchong Strategic Cooperation with Local Universities Foundation of technology
ID : 20SXQT0305
Organisme : Medical Research project of Sichuan Medical Association
ID : S21061
Organisme : The Primary Health Development Research Center of Sichuan Province Program
ID : SWFZ21-C-98

Informations de copyright

© 2023. The Author(s).

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Auteurs

Xiang Cai (X)

Department of Urology, Affiliated Hospital of North Sichuan Medical College, No. 1 Maoyuan South Road, Sichuan, 637000, Nanchong, China.

Xi Duan (X)

Department of Dermatovenereology, Affiliated Hospital of North Sichuan Medical College, No. 1 Maoyuan South Road, Sichuan, 637000, Nanchong, China.

Tielong Tang (T)

Department of Urology, Affiliated Hospital of North Sichuan Medical College, No. 1 Maoyuan South Road, Sichuan, 637000, Nanchong, China.

Shu Cui (S)

Department of Urology, Affiliated Hospital of North Sichuan Medical College, No. 1 Maoyuan South Road, Sichuan, 637000, Nanchong, China.

Tao Wu (T)

Department of Urology, Affiliated Hospital of North Sichuan Medical College, No. 1 Maoyuan South Road, Sichuan, 637000, Nanchong, China. alhawking@nsmc.edu.cn.
ORCID: 0000-0002-4441-2010

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › JMJD2A participates in cytoskeletal remodeling...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › JMJD2A participates in cytoskeletal remodeling...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › JMJD2A participates in cytoskeletal remodeling...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › JMJD2A participates in cytoskeletal remodeling...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Terpènes › Diterpènes › Taxoïdes › Docetaxel › JMJD2A participates in cytoskeletal remodeling...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › JMJD2A participates in cytoskeletal remodeling...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › microARN › JMJD2A participates in cytoskeletal remodeling...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › Tumeurs prostatiques résistantes à la castration › JMJD2A participates in cytoskeletal remodeling...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Tubuline › JMJD2A participates in cytoskeletal remodeling...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Oxygénases › Dioxygenases › Jumonji Domain-Containing Histone Demethylases › JMJD2A participates in cytoskeletal remodeling...