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pmid:36601001
CCNB1 and AURKA are critical genes for prostate cancer progression and castration-resistant prostate cancer resistant to vinblastine.
Xi Chen · Junjie Ma · Xin'an Wang · Tong Zi · Duocheng Qian · Chao Li · Chengdang Xu
Frontiers in endocrinology · 2022 doi:10.3389/fendo.2022.1106175
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Complete file
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So, androgen deprivation therapy (ADT) is effective for treating PCa. However, patients will develop castration-resistant prostate cancer (CRPC) stage after ADT. Many other treatments for CRPC exist, including chemotherapy. Vinblastine, a chemotherapeutic drug, is used to treat CRPC. However, patients will develop resistance to vinblastine. Genetic alterations have been speculated to play a critical role in CRPC resistance to vinblastine; however, its mechanism remains unclear.\nMethods: Various databases, such as Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Chinese Prostate Cancer Genome and Epigenome Atlas (CPGEA), were used to collect the RNA-sequence data of PCa and CRPC patients and vinblastine-resistant PCa cells. Using online tools, Metascape and TIMER, the pathways and immune infiltration associated with vinblastine resistance-related genes in PCa were analyzed. The function of these genes was verified in clinical samples and CRPC cells.\nResults: Using GSE81277 dataset, we collected the RNA-sequence data of vinblastine sensitive and resistant LNCaP cells and found nine genes (CDC20, LRRFIP1, CCNB1, GPSM2, AURKA, EBLN2, CCDC150, CENPA and TROAP) that correlated with vinblastine resistance. Furthermore, CCNB1, GPSM2 and AURKA were differently expressed between normal prostate and PCa tissues, even influencing PCa progression. The GSE35988 dataset revealed that CCNB1 and AURKA were upregulated in PCa and CRPC samples. Various genes were also found to affect the survival status of PCa patients based on TCGA. These genes were also related to immune cell infiltration. Finally, we verified the function of CCNB1 and AURKA and observed that they were upregulated in PCa and CRPC clinical samples and increased the sensitivity of CRPC cells to vinblastine.\nConclusion: CCNB1 and AURKA are central to CRPC resistance to vinblastine and affect PCa progression.", "claims": [{"id": "claim-method", "statement": "Comparisons between two groups were performed using the Wilcoxon test, and the Kruskal–Wallis test was employed for comparisons between more than two groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36601001", "locator": "sections[16] \"2.14 Statistical analysis\" paragraph 2", "quote": "Comparisons between two groups were performed using the Wilcoxon test, and the Kruskal–Wallis test was employed for comparisons between more than two groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/supplementary material. 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The cells were cultured in a humid environment with 5% CO2 and 95% air", "t to vinblastine. C4-2 PCa cells, which were cultured from LNCaP cells and grown in an environment"], "order_basis": "paper_text_order:2356", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["rved in 22Rv1 cells ( Figure S5B ). Next, we transfected the specific knockdown lentivirus into C4-2", "(C) and AURKA (D) when different lentivirus transfected into C4-2 CRPC cells. (E) The protein level", "of CCNB1 and AURKA when different lentivirus transfected into C4-2 CRPC cells. 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