CCNB1 and AURKA are critical genes for prostate cancer progression and castration-resistant prostate cancer resistant to vinblastine

Abstract

BackgroundProstate cancer (PCa) is a common malignancy occurring in men. As both an endocrine and gonadal organ, prostate is closely correlated with androgen. 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.MethodsVarious 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.ResultsUsing 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.ConclusionCCNB1 and AURKA are central to CRPC resistance to vinblastine and affect PCa progression.

Exploration of the influence of GOLGA8B on prostate cancer progression and resistance of castration-resistant prostate cancer to cabazitaxel

“…Chemotherapy has demonstrated its effectiveness in treating CRPC. Drugs such as docetaxel and vinblastine have been employed in CRPC treatment for improving patient survival rates (13). Docetaxel, as an e cacious therapeutic medication, can extend survival durations and enhance the e cacy of ADT in CRPC treatment (19,20).…”

“…Genetic alterations have been established as pivotal contributors to PCa resistance to chemotherapy drugs. Several studies have indicated that genetic alterations represent a crucial factor in PCa resistance to chemotherapeutic agents such as docetaxel and vinblastine (13)(14)(15). Furthermore, additional research has revealed genetic alterations as an underlying cause of PCa resistance to cabazitaxel.…”

“…Genetic alterations have emerged as signi cant contributors to resistance to chemotherapeutic drugs in PCa. Many studies have shown the pivotal role of genetic alterations as a fundamental factor underlying chemotherapy resistance in PCa, notably for drugs like docetaxel and vinblastine (13)(14)(15). Furthermore, research has highlighted that certain gene mutations can cause resistance to cabazitaxel in PCa (16,17).…”

ESCO2 promotes the proliferation of hepatocellular carcinoma through PI3K/AKT/ mTOR signaling pathway

“…The appropriate regulation of the G2/M transition phase depends on the presence of CCNB1 (Cyclin B1), which is located on 5q13.2. CCNB1 is aberrantly expressed in a number of malignancies and highly related with patient prognosis [26,27]. HCC tissues displayed considerably higher levels of CCNB1, and HCC cell proliferation may be suppressed by CCNB1 knockdown.…”

High expression of CCNB2 is an independent predictive poor prognostic biomarker and correlates with immune infiltrates in breast carcinoma

“…The aberrant expression of cyclin family members frequently contributes to tumorigenesis. For example, high cyclin B1 (CCNB1) expression affects prostate cancer development and elicits tumor resistance [ 22 ]. Similarly, cyclin E1 (CCNE1) is a potential target for ovarian carcinoma treatment [ 23 ].…”