Prolonged survival in pancreatic cancer patients with increased regucalcin gene expression: Overexpression of regucalcin suppresses the proliferation in human pancreatic cancer MIA PaCa-2 cells in vitro

Yamaguchi, Masayoshi; Osuka, Satoru; Weitzmann, M. Neale; El‐Rayes, Bassel F.; Miyake, Shoji; Murata, Takeshi

doi:10.3892/ijo.2016.3409

Cited by 36 publications

(65 citation statements)

References 37 publications

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“…By contrast, we observed initial decreases, followed by increase of some proteins, including BDH1, FGG, PAH, PTGR2, PSMA1, KRT8, NNMT, ANXA3, SUOX, AGT, and COQ9. Among them, RGN, PSMB9, and AGT are involved in functions related to oxidative stress. These proteins exhibited fluctuations in expression, and are presumed to act as potential stress‐response mediators.…”

Section: Discussionmentioning

confidence: 99%

“…RGN is a novel tumour suppressor involved in controlling intercellular signalling pathways and essential biological processes, such as oxidative stress response, metabolism, cell proliferation, and apoptosis. 29,30 The antioxidant properties of RGN includes its reduction of oxidative reactions, and enhance anti-oxidation. 29 In this study, RGN (spot 4) showed initial increase in expression, followed by decrease during increased training intensity (Figure 2).…”

Section: Three Kinds Of Differentially Expressed Proteinsmentioning

confidence: 99%

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Proteomic response of the rat liver in differential swimming modes

Chen

Yang

Wang

et al. 2018

Clin Exp Pharma Physio

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Moderate exercise helps improve competition results, providing a balanced muscle tone and biochemical activity, whereas excessive training disrupts the balance between training and recovery, causes harm to the organism, and leads to overtraining syndrome (OTS). To explore the mechanisms of different protein expressions during training and acquisition of immunity, we used proteomic analyses to investigate the differences of liver-protein expressions between 2 swimming modes. Sprague-Dawley rats were randomly divided into control (CT), fatigue training (FT), and exhaustive training (ET) groups, and liver tissues from each group were subjected to 2-dimensional electrophoresis (2DE). A total of 4518 protein spots were detected in 9 replicates, and 45 protein spots exhibited a >2-fold difference in expression (P < .05), 31 of which was successfully identified by mass spectrometry. SERPINA3K expression decreased markedly during 2 stages from CT → FT and FT → ET, while DDT, RHOT1, and RBP4 decreased significantly only from CT → ET but not from the former 2 stages. By contrast, KRT8, PCBD1, KRT18, PRDX1, and ACY1A showed significant >2-fold increase in expression in either the CT → FT or FT → ET stages. Bioinformatic analyses showed that among the identified proteins, 30.2%, 54.18%, and 15.62% were involved in biological processes, molecular functions, and cell composition, respectively. Notably, PCBD1, PRDX1, and PPP1CB were involved in redox processes, while PPP1CB was only expressed in the FT group. RGN, PSMB9, and AGT, commonly recognized as oxidative stress biomarkers, may involve in regulating homeostasis in the locomotor mode and may provide diagnostic criteria for the occurrence and prevention of exercise-induced fatigue and OTS.

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Section: Discussionmentioning

confidence: 99%

Section: Three Kinds Of Differentially Expressed Proteinsmentioning

confidence: 99%

Proteomic response of the rat liver in differential swimming modes

Chen

Yang

Wang

et al. 2018

Clin Exp Pharma Physio

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“…We have demonstrated that survival in pancreatic cancer patients is prolonged in subjects with increased regucalcin gene expression (22). Furthermore, overexpression of the human regucalcin gene suppresses the proliferation of human pancreatic cancer MIA PaCa-2 cells in vitro (22). Taken together the data suggest that regucalcin may play a potential role as a suppressor of human carcinogenesis.…”

Section: Increased Regucalcin Gene Expression Extends Survival In Brementioning

confidence: 91%

“…Regucalcin has been reported to be downregulated in human tumor tissues in vivo (19)(20)(21). We have demonstrated that survival in pancreatic cancer patients is prolonged in subjects with increased regucalcin gene expression (22). Furthermore, overexpression of the human regucalcin gene suppresses the proliferation of human pancreatic cancer MIA PaCa-2 cells in vitro (22).…”

Section: Increased Regucalcin Gene Expression Extends Survival In Brementioning

confidence: 92%

Increased regucalcin gene expression extends survival in breast cancer patients: Overexpression of regucalcin suppresses the proliferation and metastatic bone activity in MDA-MB-231 human breast cancer cells in vitro

Yamaguchi

Osuka

Weitzmann

et al. 2016

International Journal of Oncology

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Abstract. Human breast cancer is highly metastatic to bone and drives bone turnover. Breast cancer metastases cause osteolytic lesions and skeletal damage that leads to bone fractures. Regucalcin, which plays a pivotal role as an inhibitor of signal transduction and transcription activity, has been suggested to act as a suppressor of human cancer. In the present study, we compared the clinical outcome between 44 breast cancer patients with higher regucalcin expression and 43 patients with lower regucalcin expression. Prolonged relapse-free survival was identified in the patients with increased regucalcin gene expression. We further demonstrated that overexpression of full length, but not alternatively spliced variants of regucalcin, induces G1 and G2/M phase cell cycle arrest, suppressing the proliferation of MDA-MB-231 cells, a commonly used in vitro model of human breast cancer that metastasize to bone causing osteolytic lesions. Overexpression of regucalcin was found to suppress multiple signaling pathways including Akt, MAP kinase and SAPK/JNK, and NF-κB p65 and β-catenin along with increased p53, a tumor suppressor, and decreased K-ras, c-fos and c-jun. Moreover, we found that co-culture of regucalcin-overexpressing MDA-MB-231 cells with mouse bone marrow cells prevented enhanced osteoclastogenesis and suppressed mineralization in mouse bone marrow cells in vitro. Taken together, the present study suggests that regucalcin may have important anticancer properties in human breast cancer patients. Mechanistically, these effects are likely mediated through suppression of multiple signaling pathways, upregulation of p53 and downregulation of oncogenes leading to anti-proliferative effects and reduced metastases to bone, a phenotype associated with poor clinical outcome.

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“…Furthermore, RGN may act as a suppressor protein that mitigates human carcinogenesis [16]. Previously, we showed that RGN mRNA is downregulated in human tumor tissues in vivo [17], and subsequently, increased RGN gene expression is associated with prolonged survival of patients with pancreatic cancer, breast cancer, and hepatocarcinoma [18][19][20]. Moreover, the overexpression of human RGN suppressed the proliferation of human pancreatic cancer PaCa-2 cells, human breast cancer MDA-MB-231 cells, and human hepatocellular carcinoma HepG2 cells [18][19][20].…”

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confidence: 99%

Regucalcin confers resistance to amyloid‐β toxicity in neuronally differentiated PC12 cells

et al. 2018

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Amyloid‐β (Aβ), a primary component of amyloid plaques, has been widely associated with the pathogenesis of Alzheimer's disease. The Ca 2+ ‐binding protein regucalcin (RGN) plays multiple roles in maintaining cell functions by regulating intracellular calcium homeostasis, various signaling pathways, and gene expression systems. Here, we investigated the functional role of RGN against Aβ‐induced cytotoxicity in neuronally differentiated PC 12 cells. Overexpression of RGN reduced Aβ‐induced apoptosis by reducing mitochondrial dysfunction and caspase activation. It also attenuated Aβ‐induced reactive oxygen species production and oxidative damage and decreased Aβ‐induced nitric oxide (NO) overproduction, upregulation of inducible NO synthase by nuclear factor‐κB, and nitrosative damage. Interestingly, the genetic disruption of RGN increased the susceptibility of neuronally differentiated PC 12 cells to Aβ toxicity. Thus, RGN possesses antioxidant activity against Aβ‐induced oxidative and nitrosative stress and may play protective roles against Aβ‐induced neurotoxicity in Alzheimer's disease.

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Prolonged survival in pancreatic cancer patients with increased regucalcin gene expression: Overexpression of regucalcin suppresses the proliferation in human pancreatic cancer MIA PaCa-2 cells in vitro

Cited by 36 publications

References 37 publications

Proteomic response of the rat liver in differential swimming modes

Proteomic response of the rat liver in differential swimming modes

Increased regucalcin gene expression extends survival in breast cancer patients: Overexpression of regucalcin suppresses the proliferation and metastatic bone activity in MDA-MB-231 human breast cancer cells in vitro

Regucalcin confers resistance to amyloid‐β toxicity in neuronally differentiated PC12 cells

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