Abstract:H1 histamine receptor (H1HR) belongs to the family of rhodopsin-like G-protein-coupled receptors. Recent studies have shown that H1HR expression is increased in several types of cancer. However, its functional roles in tumor progression remain largely unknown, especially in hepatocellular carcinoma (HCC). We found that H1HR is frequently unregulated in HCC, which is significantly associated with both recurrence-free survival and overall survival in HCC patients. Functional experiments revealed that H1HR promot… Show more
“…6,7,16 Zhao et al reported that upregulated HRH1 promoted tumor progression and contributed to poor prognosis in HCC. 8 Histamine and histamine receptors have been identified as critical molecules during inflammation and carcinogenesis, which might be potential molecular target for cancer therapeutics. 6,17 Abnormal expression of HRH3 has been reported in different types of cancer, including HCC, cholangiocarcinoma, melanoma, pancreatic, and breast cancer.…”
Section: Discussionmentioning
confidence: 99%
“…5 Abnormal expression levels of histamine receptors have been reported in different types of human cancers. [5][6][7][8][9] Zhao et al reported that upregulation of HRH1 promoted tumor progression and contributed to poor prognosis in hepatocellular carcinoma. 8 Tanaka demonstrated that both HRH2 antagonist cimetidine and HRH3 antagonist clobenpropit attenuated inflammation-associated colorectal carcinogenesis in male ICR mice.…”
Section: Introductionmentioning
confidence: 99%
“…[5][6][7][8][9] Zhao et al reported that upregulation of HRH1 promoted tumor progression and contributed to poor prognosis in hepatocellular carcinoma. 8 Tanaka demonstrated that both HRH2 antagonist cimetidine and HRH3 antagonist clobenpropit attenuated inflammation-associated colorectal carcinogenesis in male ICR mice. 6 Meng et al reported that activation of HRH4 suppressed human cholangiocarcinoma progression by disruption of epithelial mesenchymal transition and tumor metastasis.…”
Background: The histamine H3 receptor (HRH3) is mainly expressed in areas of the brain involved in the regulation of the release of various neurotransmitters. Recent studies have shown that HRH3 expression is increased in several types of carcinomas. However, the functional roles and underlying molecular mechanism by which HRH3 regulates cell survival in hepatocellular carcinoma (HCC) remain unknown. Methods: The mRNA and protein expression level of target genes were evaluated by qRT-PCR, Western blot and immunohistochemistry, respectively. Cell viability and cell proliferation activity were assessed by MTS assay and EdU incorporation assay. Cell apoptosis and cell cycle were assessed by flow cytometry analysis. A xenograft mouse model was constructed to investigate the effect of HRH3 on tumor growth in vivo. Results: Our results indicated that HRH3 was significantly upregulated in HCC, which promoted cell survival by accelerating cell proliferation and inhibiting cell apoptosis. Our results also showed that HRH3 in HCC downregulated the expression of cyclin-dependent kinase inhibitor p21 (CDKN1A) to promote G1-S phase transition by inactivating the cAMP/ PKA/CREB pathway, which finally contributed to the malignant growth of HCC. Conclusion: Our findings indicated that HRH3 functioned in promoting HCC survival by inactivating the cAMP/PKA/CREB pathway to downregulate CDKN1A expression. Thus, HRH3 might serve as a potential therapeutic target in HCC treatment.
“…6,7,16 Zhao et al reported that upregulated HRH1 promoted tumor progression and contributed to poor prognosis in HCC. 8 Histamine and histamine receptors have been identified as critical molecules during inflammation and carcinogenesis, which might be potential molecular target for cancer therapeutics. 6,17 Abnormal expression of HRH3 has been reported in different types of cancer, including HCC, cholangiocarcinoma, melanoma, pancreatic, and breast cancer.…”
Section: Discussionmentioning
confidence: 99%
“…5 Abnormal expression levels of histamine receptors have been reported in different types of human cancers. [5][6][7][8][9] Zhao et al reported that upregulation of HRH1 promoted tumor progression and contributed to poor prognosis in hepatocellular carcinoma. 8 Tanaka demonstrated that both HRH2 antagonist cimetidine and HRH3 antagonist clobenpropit attenuated inflammation-associated colorectal carcinogenesis in male ICR mice.…”
Section: Introductionmentioning
confidence: 99%
“…[5][6][7][8][9] Zhao et al reported that upregulation of HRH1 promoted tumor progression and contributed to poor prognosis in hepatocellular carcinoma. 8 Tanaka demonstrated that both HRH2 antagonist cimetidine and HRH3 antagonist clobenpropit attenuated inflammation-associated colorectal carcinogenesis in male ICR mice. 6 Meng et al reported that activation of HRH4 suppressed human cholangiocarcinoma progression by disruption of epithelial mesenchymal transition and tumor metastasis.…”
Background: The histamine H3 receptor (HRH3) is mainly expressed in areas of the brain involved in the regulation of the release of various neurotransmitters. Recent studies have shown that HRH3 expression is increased in several types of carcinomas. However, the functional roles and underlying molecular mechanism by which HRH3 regulates cell survival in hepatocellular carcinoma (HCC) remain unknown. Methods: The mRNA and protein expression level of target genes were evaluated by qRT-PCR, Western blot and immunohistochemistry, respectively. Cell viability and cell proliferation activity were assessed by MTS assay and EdU incorporation assay. Cell apoptosis and cell cycle were assessed by flow cytometry analysis. A xenograft mouse model was constructed to investigate the effect of HRH3 on tumor growth in vivo. Results: Our results indicated that HRH3 was significantly upregulated in HCC, which promoted cell survival by accelerating cell proliferation and inhibiting cell apoptosis. Our results also showed that HRH3 in HCC downregulated the expression of cyclin-dependent kinase inhibitor p21 (CDKN1A) to promote G1-S phase transition by inactivating the cAMP/ PKA/CREB pathway, which finally contributed to the malignant growth of HCC. Conclusion: Our findings indicated that HRH3 functioned in promoting HCC survival by inactivating the cAMP/PKA/CREB pathway to downregulate CDKN1A expression. Thus, HRH3 might serve as a potential therapeutic target in HCC treatment.
“…MCs are able to express and secrete MMP2 and MMP9 to liberate VEGF and fibroblast growth factor (bFGF) from the ECM and thus to stimulate angiogenesis 52 . Also, it has been found that the interaction between MCs‐secreted histamine and its receptor 1, H1 (H1HR), can drive cell‐cycle progression, MMP2 production, and suppression of apoptosis 53 . In addition to tumor enhancing characteristics, studies have suggested that MCs also have immunomodulatory effects on cancer cells 54 .…”
Advances in immunotherapy have led to durable and long‐term benefits in a subset of patients across a number of solid tumor types. Understanding of the subsets of patients that respond to immune checkpoint inhibitors at the cellular level, and in the context of their tumor microenvironment (TME) is becoming increasingly important. The TME is composed of a heterogeneous milieu of tumor and immune cells. The immune landscape of the TME can inhibit or promote tumor initiation and progression; thus, a deeper understanding of tumor immunity is necessary to develop immunotherapeutic strategies. Recent developments have focused on characterizing the TME immune contexture (type, density, and function) to discover mechanisms and biomarkers that may predict treatment outcomes. This has, in part, been powered by advancements in spatial characterization technologies. In this review article, we address the role of specific immune cells within the TME at various stages of tumor progression and how the immune contexture determinants affecting tumor growth are used therapeutically.
“…Although the mechanism of action of miR-940 is still unclear, current studies have shown that miR-940 not only interregulates with some other non-coding RNAs ( Figure 4 ), but it also downregulates the expression of 29 genes ( Table 1 ). By regulating the functions of many downstream genes, miR-940 can affect cell proliferation, 21 migration, 23 invasion, 15 apoptosis, 11 cell cycle, 35 EMT, 40 osteogenic differentiation, 12 and other biological processes ( Figure 2 ). Figure 2 miR-940 affects the biological process of cells through target genes miR-940 affects cell proliferation, migration, invasion, apoptosis, EMT, cell cycle, and osteogenic differentiation by regulating target genes.…”
miR-940 is a microRNA located on chromosome 16p13.3, which has varying degrees of expression imbalance in many diseases. It binds to the 3′ untranslated region (UTR) and affects the transcription or post-transcriptional regulation of target protein-coding genes. For a diversity of cellular processes, including cell proliferation, migration, invasion, apoptosis, epithelial-to-mesenchymal transition (EMT), cell cycle, and osteogenic differentiation, miR-940 can affect them not only by regulating protein-coding genes but also long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in pathways. Intriguingly, miR-940 participates in four pathways that affect cancer development, including the Wnt/β-catenin pathway, mitogen-activated protein kinase (MAPK) pathway, PD-1 pathway, and phosphatidylinositol 3-kinase (PI3K)-Akt pathway. Importantly, the expression of miR-940 is intimately correlated with the diagnosis and prognosis of tumor patients, as well as to the efficacy of tumor chemotherapy drugs. In conclusion, our main purpose is to outline the expression of miR-940 in various diseases and the molecular biological and cytological functions of target genes in order to reveal its potential diagnostic and prognostic value as well as its predictive value of drug efficacy.
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