Analysis of key genes reveal lysine demethylase 5B promotes prostate cancer progression

Abstract

Prostate cancer (PCa) is one of the most common types of cancer in males globally. However, the molecular mechanisms underlying PCa progression remain largely unclear. In the present study, Gene Expression Omnibus (GEO) datasets and datasets from The Cancer Genome Atlas (TCGA) were used to analyze the expression of lysine demethylase 5B (KDM5B) in PCa. Proliferation, cell cycle and migration assays were used to detect the functional roles of KDM5B. It was found KDM5B was upregulated in PCa tissues by analyzing GEO and TCGA datasets. KDM5B knockdown significantly suppressed proliferation and cell cycle progression in PCa cells. In additional, KDM5B knockdown inhibited PCa cell migration. By analyzing a TCGA dataset, KDM5B was found to be upregulated in patients at N1 stage compared with N0 stage PCa, in patients at T3+T4 stages compared with T2 stage and in patients with Gleason score ≥8 compared with those with score ≤7. Kaplan-Meier analysis revealed that higher expression of KDM5B was associated with shorter biochemical recurrence-free survival and overall survival time in patients with PCa. These results suggest that expression of KDM5B may serve as a biomarker to predict the outcome of PCa.

The KDM5B and KDM1A lysine demethylases cooperate in regulating androgen receptor expression and signalling in prostate cancer

“…The functional significance of KDM5B in PCa cells, and the therapeutic feasibility and clinical utility of KDM5 inhibitors to treat PCa remain poorly understood. There is also increasing evidence that KDM5B also plays complex and context specific roles in prostate development, homeostasis and carcinogenesis ( Xiang et al, 2007 ; Klein et al, 2014 ; Li et al, 2020 ; Liu et al, 2020 ; Yang et al, 2020 ).…”

“…Recent studies utilizing a prostate specific KDM5B conditional knockout mouse model indicates KDM5B loss contributes to prostate hyperplasia ( Liu et al, 2020 ). However, KDM5B mRNA expression is higher in PCa patient specimens ( Liu et al, 2020 ) and KDM5B promotes proliferation and invasion and is associated with worse clinical parameters of poorer outcomes ( Yang et al, 2020 ). Consistent with a pro-oncogenic function for KDM5B, prostate-specific depletion of KDM5B and PTEN in the mouse prostate epithelium and PCa cell lines supports a role for KDM5B in activating the PI3K/AKT pathway in prostate carcinogenesis ( Li et al, 2020 ).…”

Overcoming radio-resistance in esophageal squamous cell carcinoma via hypermethylation of PIK3C3 promoter region mediated by KDM5B loss

“…In addition, silencing of KDM5B blocked oncogenicity, stemness and augmented radiation sensitivity in human oral carcinoma [ 12 ]. Moreover, KDM5B knockdown significantly suppressed proliferation and decreased the proportion of cells in S and G2/M phase of prostate cancer cells [ 22 ]. Bak protein was upregulated, whereas Bcl-2 was downregulated in the KDM5B-knockdown cells, indicating KDM5B maintained head and neck squamous cell carcinoma survival by regulating Bcl family members [ 23 ].…”

KDM5B expression in cisplatin resistant neuroblastoma cell lines

“…The mechanism of the relationship between KDM5B and the cell cycle is not yet known, PI3K-AKT pathway activation (41), BRCA1 (42) and transcription factors E2F1 and E2F2 (43) are expected to be affected, but other mechanisms are also possible. In a series of tumors, its silence inhibits and reduces the percentage of cells in S phase, for example in prostate cancer (44), hepatocellular carcinoma (43), bladder cancer and small cell lung carcinoma (33) or acute lymphoblastic leukemia (42). On the other hand, in melanoma it has the opposite effect, i.e.…”