Histone methyltransferase KMT2D promotes prostate cancer progression through paracrine IL-6 signaling

Zhang, Jianqiang; Ye, Yuedian; Xu, Zhuofan; Luo, Mayao; Wu, Chenwei; Zhang, Yifan; Lv, Shidong; Wei, Qiang

doi:10.1016/j.bbrc.2023.02.083

Cited by 8 publications

(5 citation statements)

References 45 publications

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“…In the comparison analysis between the disease control group and the prostate cancer group, our study found that the concentration of IL-6 was signi cantly higher in the prostate cancer group than in the disease control group, which suggests a potential role of IL-6 in prostate cancer progression. This nding is consistent with previous studies that reported increased IL-6 levels in the peripheral blood of prostate cancer patients [28][29][30]. IL-6 is known to play a critical role in prostate-mediated immune responses and can stimulate humoral and cellular immune responses by acting on B and T lymphocytes, promoting their growth and differentiation, and participating in in ammation induced by follicular Th cells [27,28,31].…”

Section: Discussionsupporting

confidence: 92%

Evaluation of the Clinical Application Value of Cytokine Expression Profiles in the Differential Diagnosis of Prostate Cancer

Chen,

Liu,

Chen

et al. 2024

Preprint

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Background The significance of tumor-secreted cytokines in tumor development has gained substantial attention. Nevertheless, the precise role of tumor-related inflammatory cytokines in prostate cancer (PCa) remains ambiguous. Objectives To gain deeper insights into the inflammatory response in the process of PCa. Methods A total of 141 cases were collected, including 70 cases of prostate hyperplasia and 9 cases of prostatitis as disease control, 41 cases of postoperative prostate cancer and 21 cases of prostate cancer as PCa group. Additionally, 31 patients undergoing physical examinations during the same period were collected as the healthy control. The levels of 12 inflammatory cytokines in peripheral blood samples were analyzed using flow cytometric bead array technology. The levels of total prostate-specific antigen (TPSA) and free prostate-specific antigen (FPSA) in peripheral blood samples were analyzed using electrochemiluminescence technology. Results Our results showed that serum IL-5, IL-6, IL-8 levels were significantly increased in PCa group compared to those in the control group (all p < 0.05). While, the level of IL-2, IL-10, TNF-α, IL-1β, IL-12p70, and IFN-α were lower in PCa than in healthy control. The concentration of IL-6 decreased but the concentrations of IL-4, IL-10, TNF-α, and IL-17A increased after surgery, showing significant differences (p < 0.05). The differential upregulation of IL-6 and IL-8 in peripheral blood have diagnostic efficacy in PCa patients. Conclusion The peripheral blood cytokines are closely associated with the occurrence and development of prostate cancer, especially the serum levels of IL-6 and IL-8 may be useful as potential predictors of PCa diagnosis.

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Section: Discussionsupporting

confidence: 92%

Evaluation of the Clinical Application Value of Cytokine Expression Profiles in the Differential Diagnosis of Prostate Cancer

Chen,

Liu,

Chen

et al. 2024

Preprint

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“…Our study revealed a significant elevation in IL-6 concentration within the prostate cancer group compared to the disease control group, indicating a potential involvement of IL-6 in prostate cancer progression. This observation aligns with prior research documenting heightened IL-6 levels in the peripheral blood of individuals with prostate cancer [ 29 – 31 ]. IL-6 is recognized for its pivotal role in prostate-mediated immune responses, exerting influence on both humoral and cellular immune responses.…”

Section: Discussionsupporting

confidence: 91%

Evaluation of the clinical application value of cytokine expression profiles in the differential diagnosis of prostate cancer

Chen,

Liu,

Chen

et al. 2024

Cancer Immunol Immunother

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Background The significance of tumor-secreted cytokines in tumor development has gained substantial attention. Nevertheless, the precise role of tumor-related inflammatory cytokines in prostate cancer (PCa) remains ambiguous. Objectives To gain deeper insights into the inflammatory response in the process of PCa. Methods A total of 233 cases were collected, including 80 cases of prostate hyperplasia as disease control, 65 cases of postoperative prostate cancer and 36 cases of prostate cancer as PCa group. Additionally, 52 patients undergoing physical examinations during the same period were collected as the healthy control. The levels of 12 inflammatory cytokines in peripheral blood samples were analyzed using flow cytometric bead array technology. The levels of total prostate-specific antigen (TPSA) and free prostate-specific antigen (FPSA) in peripheral blood samples were analyzed using electrochemiluminescence technology. Results Our findings revealed significant increases in serum IL-8 levels in PCa group compared to the healthy control group. Additionally, IL-6, IL-10, IFN-γ and IL-12p70 levels were markedly elevated in the PCa group compared to the disease control group (all p < 0.05). Conversely, the level of IL-4, TNF-α, IL-1β, IL-17A and IFN-α were lower in the PCa group compared to those in control group. Following surgery, the concentration of IL-6 decreased; whereas, the concentrations of IL-4, TNF-α, IL-17A, IL-1β, IL-12p70, and IFN-α increased, demonstrating significant differences (p < 0.05). The differential upregulation of IL-6 or downregulation of IL-17A in peripheral blood exhibited diagnostic efficacy in PCa patients. Moreover, we observed a significant increase in IL-17A levels, accompanied by decreased of IL-2, IL-4, IL-10, TNF-a, IFN-γ, IL-1β, and IL-12P70 in patients with distant metastasis. Conclusion The peripheral blood cytokines are closely associated with the occurrence and development of prostate cancer, especially the serum levels of IL-6 and IL-17A may be useful as potential predictors of PCa diagnosis.

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“…Noteworthy evidence has shown that the loss of KMT2D is linked to several and contrasting cancer mechanisms, such as decreased expression of the tumor suppressors PTEN and TP53 in bladder cancer 89 ; inhibition of proliferation, migration and invasion in papillary thyroid carcinoma cells, with reduced expression of NCOA6 and THRB 84 ; activation of EGFR and ERBB2 with repression of multiple receptor‐like protein tyrosine phosphatases (RPTPs), which activate oncogenic RTK‐RAS signaling in lung squamous cell carcinoma, promoting tumor growth 90 . KMT2D also appears to play important roles in cell–cell communications via IL‐6 which leads to the establishment of a tumor‐supportive microenvironment in prostate cancer and may even serve as an indirect regulator of cancer cell proliferation 91 . Moreover, KMT2D knockout in the esophageal squamous cell carcinoma cell line prevented cell proliferation and migration, causing cell cycle arrest at G1 stage 92 …”

Section: Discussionmentioning

confidence: 99%

“…90 KMT2D also appears to play important roles in cell-cell communications via IL-6 which leads to the establishment of a tumor-supportive microenvironment in prostate cancer and may even serve as an indirect regulator of cancer cell proliferation. 91 Moreover, KMT2D knockout in the esophageal squamous cell carcinoma cell line prevented cell proliferation and migration, causing cell cycle arrest at G1 stage. 92 KMT2C is a commonly mutated gene in many cancer types, which has been associated with worse outcomes.…”

Section: Genetic Alterationsmentioning

confidence: 99%

KMT2 (MLL) family of methyltransferases in head and neck squamous cell carcinoma: A systematic review

da Silva Santos,

de Carvalho Abreu,

Martins da Silva

et al. 2023

Head & Neck

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BackgroundThe involvement of the KMT2 methyltransferase family in the pathogenesis of head and neck squamous cell carcinoma (HNSCC) remains elusive.MethodThis study adhered to the PRISMA guidelines, employing a search strategy in the LIVIVO, PubMed, Scopus, Embase, Web of Science, and Google Scholar databases. The methodological quality of the studies was assessed by the Joanna Briggs Institute.ResultsA total of 33 studies involving 4294 individuals with HNSCC were included in this review. The most important alteration was the high mutational frequency in the KMT2C and KMT2D genes, with reported co‐occurrence. The expression of the KMT2D gene exhibited considerable heterogeneity across the studies, while limited data was available for the remaining genes.ConclusionsKMT2C and KMT2D genes seem to have tumor suppressor activities, with involvement of cell cycle inhibitors, regulating different pathways that can lead to tumor progression, disease aggressiveness, and DNA damage accumulation.

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Histone methyltransferase KMT2D promotes prostate cancer progression through paracrine IL-6 signaling

Cited by 8 publications

References 45 publications

Evaluation of the Clinical Application Value of Cytokine Expression Profiles in the Differential Diagnosis of Prostate Cancer

Evaluation of the Clinical Application Value of Cytokine Expression Profiles in the Differential Diagnosis of Prostate Cancer

Evaluation of the clinical application value of cytokine expression profiles in the differential diagnosis of prostate cancer

KMT2 (MLL) family of methyltransferases in head and neck squamous cell carcinoma: A systematic review

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