Inhibition of Transient Receptor Potential Melastain 7 Enhances Apoptosis Induced by TRAIL in PC-3 cells

Lin, Chang-Ming,Ma, Ji-Min,Zhang, Li,Hao, Zong-Yao,Zhou, Jun,Zhou, Zhen-Yu,Shi, Hao-Qiang,Zhang, Yi-Fei,Shao, En-Ming,Liang, Chao-Zhao Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.10

Transient receptor potential melastain 7 (TRPM7) is a bifunctional protein with dual structure of both ion channel and protein kinase, participating in a wide variety of diseases including cancer. Recent researches have reported the mechanism of TRPM7 in human cancers. However, the correlation between TRPM7 and prostate cancer (PCa) has not been well studied. The objective of this study was to investigate the potential the role of TRPM7 in the apoptosis of PC-3 cells, which is the key cell of advanced metastatic PCa. In this study, we demonstrated the influence and potential function of TRPM7 on the PC-3 cells apoptosis induced by TNF-related apoptosis inducing-ligand (TRAIL). The study also found a novel up-regulated expression of TRPM7 in PC-3 cells after treating with TRAIL. Suppression of TRPM7 by TRPM7 non-specific inhibitors ($Gd^{3+}$ or 2-aminoethoxy diphenylborate (2-APB) ) not only markedly eliminated TRPM7 expression level, but also increased the apoptosis of TRAIL-treated PC-3 cells, which may be regulated by the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway accompany with up-regulated expression of cleaved Caspase-3, (TRAIL-receptor 1, death receptors 4) DR4, and (TRAIL-receptor 2, death receptors 5) DR5. Taken together, our findings strongly suggested that TRPM7 was involved in the apoptosis of PC-3 cells induced by TRAIL, indicating that TRPM7 may be applied as a therapeutic target for PCa.

MicroRNA-21 Regulates the Invasion and Metastasis in Cholangiocarcinoma and May Be a Potential Biomarker for Cancer Prognosis

Huang, Qiang,Liu, Lei,Liu, Chen-Hai,You, Hao,Shao, Feng,Xie, Fang,Lin, Xian-Sheng,Hu, San-Yuan,Zhang, Chuan-Hai Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.2

Background: MicroRNAs are noncoding RNA molecules that posttranscriptionally regulate gene expression. The aim of this study was to determine the role of microRNA-21 in cholangiocarcinomas and its relationship to cholangiocarcinoma RBE cell capacity for invasion and metastasis. Methods: MicroRNA-21 expression was investigated in 41 cases of cholangiocarcinoma samples by in situ hybridization and real-time PCR. Influence on cholangiocarcinoma cell line invasion and metastasis was analyzed with microRNA-21 transfected cells. In addition, regulation of reversion-inducing-cysteine-rich protein with kazal motifs (RECK) by microRNA-21 was elucidated to identify mechanisms. Results: In situ hybridization and real-time quantitative PCR results for patients with lymph node metastasis or perineural invasion showed significantly high expression of microRNA-21 (P<0.05). There was a dramatic decrease in cholangiocarcinoma cell line invasion and metastasis ability after microRNA-21 knockdown (P<0.05). However, overexpression significantly increased invasion and metastasis (P<0.05). Real-time PCR and Western-blot analysis showed that microRNA-21 could potentially inhibit RECK expression in RBE cells. Survival analysis showed that patients with higher expression levels of microRNA-21 more often had a poor prognosis (P<0.05). Conclusions: MicroRNA-21 may play an important role in cholangiocarcinoma invasion and metastasis, suggesting that MicroRNA-21 should be further evaluated as a biomarker for predicting cholangiocarcinoma prognosis.

NAD(P)H: Quinone Oxidoreductase 1 (NQO1) C609T Gene Polymorphism Association with Digestive Tract Cancer: A Meta-analysis

Zhu, Cheng-Lin,Huang, Qiang,Liu, Chen-Hai,Lin, Xian-Sheng,Xie, Fang,Shao, Feng Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T gene polymorphisms have been reported to influence the risk for digestive tract cancer (DTC) in many studies; however, the results remain controversial and ambiguous. We therefore carried out a meta-analysis of published case-control studies to derive a more precise estimation of any associations. Electronic searches were conducted on links between this variant and DTC in several databases through April 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of associations in fixed or random effect models. Heterogeneity and publication bias were also assessed. A total of 21 case-control studies were identified, including 6,198 cases and 7,583 controls. Overall, there was a statistically significant association between the NQO1 C609T polymorphism and DTC risk (TT vs. CC: OR=1.224, 95%CI=1.055-1.421; TT/CT vs. CC: OR=1.195, 95%CI=1.073-1.330; TT vs. CT/CC: OR=1.183, 95%CI=1.029-1.359; T vs. C: OR=1.180, 95%CI=1.080-1.290). When stratified for tumor location, the results based on all studies showed the variant allele 609T might have a significantly increased risk of upper digest tract cancer (UGIC), but not colorectal cancer. In the subgroup analysis by ethnicity, we observed a significantly risk for DTC in Caucasians. For esophageal and gastric cancer, a significantly risk was found in both populations, and for colorectal, a weak risk was observed in Caucasians, but not Asians. This meta-analysis suggested that the NQO1 C609T polymorphism may increase the risk of DTC, especially in the upper gastric tract.

Protein target identifi cation of ginsenosides in skeletal muscle tissues: discovery of natural smallmolecule activators of muscle-type creatine kinase

Feiyan Chen,Kexuan Zhu,Lin Chen,Liufeng Ouyang,Cuihua Chen,Ling Gu,Yucui Jiang,Zhongli Wang,Zixuan Lin,Qiang Zhang,Xiao Shao,Jianguo Dai,Yunan Zhao 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.3

Background: Ginseng effectively reduces fatigue in both animal models and clinical trials. However, themechanism of action is not completely understood, and its molecular targets remain largely unknown. Methods: By screening for proteins that interact with the primary components of ginseng (ginsenosides)in an affinity chromatography assay, we have identified muscle-type creatine kinase (CK-MM) as a potentialtarget in skeletal muscle tissues. Results: Biolayer interferometry analysis showed that ginsenoside metabolites, instead of parent ginsenosides,had direct interaction with recombinant human CK-MM. Subsequently, 20(S)-protopanaxadiol(PPD), which is a ginsenoside metabolite and displayed the strongest interaction with CK-MM in thestudy, was selected as a representative to confirm direct binding and its biological importance. Biolayerinterferometry kinetics analysis and isothermal titration calorimetry assay demonstrated that PPDspecifically bound to human CK-MM. Moreover, the mutation of key amino acids predicted by moleculardocking decreased the affinity between PPD and CK-MM. The direct binding activated CK-MM activityin vitro and in vivo, which increased the levels of tissue phosphocreatine and strengthened the functionof the creatine kinase/phosphocreatine system in skeletal muscle, thus buffering cellular ATP, delayingexercise-induced lactate accumulation, and improving exercise performance in mice. Conclusion: Our results suggest a cellular target and an initiating molecular event by which ginsengreduces fatigue. All these findings indicate PPD as a small molecular activator of CK-MM, which can helpin further developing better CK-MM activators based on the dammarane-type triterpenoid structure.

All-trans-retinoic Acid Promotes Iodine Uptake Via Up-regulating the Sodium Iodide Symporter in Medullary Thyroid Cancer Stem Cells

Tang, Min,Hou, Yan-Li,Kang, Qiang-Qiang,Chen, Xing-Yue,Duan, Li-Qun,Shu, Jin,Li, Shao-Lin,Hu, Xiao-Li,Peng, Zhi-Ping Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

Recently, the main therapy of medullary thyroid cancer (MTC) is surgical, but by which way there is a poor prognosis with a mean survival of only 5 years. In some cases, some researchers found that it is the medullary thyroid cancer stem cells (MTCSCs) that cause metastasis and recurrence. This study aimed to eradicate MTCSCs through administration of all-trans-retinoic acid (ATRA). Here we demonstrate that MTCSCs possess stemlike properties in serum-free medium. The ABCG2, OCT4 and sodium iodide symporter (NIS) were changed by ATRA. Additionally, we found that ATRA can increase the expression of NIS in vivo. All the data suggested that ATRA could increase the iodine uptake of MTCSCs through NIS.

Protein target identification of ginsenosides in skeletal muscle tissues: discovery of natural small-molecule activators of muscle-type creatine kinase

Chen, Feiyan,Zhu, Kexuan,Chen, Lin,Ouyang, Liufeng,Chen, Cuihua,Gu, Ling,Jiang, Yucui,Wang, Zhongli,Lin, Zixuan,Zhang, Qiang,Shao, Xiao,Dai, Jianguo,Zhao, Yunan The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.3

Background: Ginseng effectively reduces fatigue in both animal models and clinical trials. However, the mechanism of action is not completely understood, and its molecular targets remain largely unknown. Methods: By screening for proteins that interact with the primary components of ginseng (ginsenosides) in an affinity chromatography assay, we have identified muscle-type creatine kinase (CK-MM) as a potential target in skeletal muscle tissues. Results: Biolayer interferometry analysis showed that ginsenoside metabolites, instead of parent ginsenosides, had direct interaction with recombinant human CK-MM. Subsequently, 20(S)-protopanaxadiol (PPD), which is a ginsenoside metabolite and displayed the strongest interaction with CK-MM in the study, was selected as a representative to confirm direct binding and its biological importance. Biolayer interferometry kinetics analysis and isothermal titration calorimetry assay demonstrated that PPD specifically bound to human CK-MM. Moreover, the mutation of key amino acids predicted by molecular docking decreased the affinity between PPD and CK-MM. The direct binding activated CK-MM activity in vitro and in vivo, which increased the levels of tissue phosphocreatine and strengthened the function of the creatine kinase/phosphocreatine system in skeletal muscle, thus buffering cellular ATP, delaying exercise-induced lactate accumulation, and improving exercise performance in mice. Conclusion: Our results suggest a cellular target and an initiating molecular event by which ginseng reduces fatigue. All these findings indicate PPD as a small molecular activator of CK-MM, which can help in further developing better CK-MM activators based on the dammarane-type triterpenoid structure.

Rho-GTPase Effector ROCK Phosphorylates Cofilin in Actin-Meditated Cytokinesis During Mouse Oocyte Meiosis

Duan, Xing,Jun-Liu,Dai, Xiao-Xin,Liu, Hong-Lin,Cui, Xiang-Shun,Kim, Nam-Hyung,Wang, Zhen-Bo,Qiang-Wang,Sun, Shao-Chen Society for the Study of Reproduction [etc.] 2014 BIOLOGY OF REPRODUCTION Vol.90 No.2

During oocyte meiosis, a spindle forms in the central cytoplasm and migrates to the cortex. Subsequently, the oocyte extrudes a small body and forms a highly polarized egg; this process is regulated primarily by actin. ROCK is a Rho-GTPase effector that is involved in various cellular functions, such as stress fiber formation, cell migration, tumor cell invasion, and cell motility. In this study, we investigated possible roles for ROCK in mouse oocyte meiosis. ROCK was localized around spindles after germinal vesicle breakdown and was colocalized with cytoplasmic actin and mitochondria. Disrupting ROCK activity by RNAi or an inhibitor resulted in cell cycle progression and polar body extrusion failure. Time-lapse microscopy showed that this may have been due to spindle migration and cytokinesis defects, as chromosomes segregated but failed to extrude a polar body and then realigned. Actin expression at oocyte membranes and in cytoplasm was significantly decreased after these treatments. Actin caps were also disrupted, which was confirmed by a failure to form cortical granule-free domains. The mitochondrial distribution was also disrupted, which indicated that mitochondria were involved in the ROCK-mediated actin assembly. In addition, the phosphorylation levels of Cofilin, a downstream molecule of ROCK, decreased after disrupting ROCK activity. Thus, our results indicated that a ROCK-Cofilinactin pathway regulated meiotic spindle migration and cytokinesis during mouse oocyte maturation.

Synergistic Effect of Bone Marrow-Derived Mesenchymal Stem Cells and Platelet-Rich Plasma in Streptozotocin-Induced Diabetic Rats

( Zhen Zhen Lian ),( Xiao Jing Yin ),( Hua Li ),( Li Li Jia ),( Xiu Zhen He ),( Yong Bo Yan ),( Nai Hua Liu ),( Ka Yiu Wan ),( Xiao Kun Li ),( Shao Qiang Lin ) 대한피부과학회 2014 Annals of Dermatology Vol.26 No.1

Background: Diabetic wounds are a major clinical challenge, because minor skin wounds can lead to chronic, unhealed ulcers and ultimately result in infection, gangrene, or even amputation. Studies on bone marrow derived mesenchymal stem cells (BMSCs) and a series of growth factors have revealed their many benefits for wound healing and regeneration. Platelet-rich plasma (PRP) may improve the environment for BMSC development and differentiation. However, whether combined use of BMSCs and PRP may be more effective for accelerating diabetic ulcer healing remains unclear. Objective: We investigated the efficacy of BMSCs and PRP for the repair of refractory wound healing in a diabetic rat model. Methods: Forty-eight rats with diabetes mellitus induced by streptozotocin were divided into four groups: treatment with BMSCs plus PRP, BMSCs alone, PRP alone, phosphate buffered saline. The rate of wound closure was quantified. A histopathological study was conducted regarding wound depth and the skin edge at 7, 14, and 28 days after surgery. Results: Wound healing rates were significantly higher in the BMSC plus PRP group than in the other groups. The immunohistochemistry results showed that the expression of platelet/endothelial cell adhesion molecule 1, proliferating cell nuclear antigen, and transforming growth factor-β1 increased significantly in the BMSC plus PRP group compared to the other treatment groups. On day 7, CD68 expression increased significantly in the wounds of the BMSC plus PRP group, but decreased markedly at day 14 compared to the controls. Conclusion: The combination of BMSCs and PRP aids diabetic wound repair and regeneration. (Ann Dermatol 26(1) 1∼10, 2014)