Frat1与β-catenin在非小细胞肺癌中表达的相关性及意义

目的探讨Frat1在肺癌组织中的表达情况以及Frat1与β-catenin在肺癌组织中表达的相关性。方法用免疫组化SP法对115例原发性非小细胞肺癌(NSCLC)患者手术标本中Frat1和β-catenin的表达进行检测,使用SPSS16.0统计软件进行分析。结果在NSCLC中,Frat1的表达与肺癌组织的低分化(P=0.035)、淋巴结转移(P=0.019)、TNM分期相关(P=0.010);β-catenin的表达与肺癌组织的低分化(P=0.017)、淋巴结转移(P=0.007)、TNM分期相关(P=0.016);Frat1的表达与β-catenin的表达有相关性(P=0.003)。结论 Frat1和β-catenin与肺癌的低分化、转移、高级别TNM分期等恶性表型有关,二者在肺癌组织中的表达有相关性,Frat1可能成为NSCLC患者靶向治疗的新靶点。     

SFRP1和SFRP2在肾细胞癌组织中的表达及其意义

目的：探讨wnt信号通路拮抗剂分泌型卷曲相关蛋白1（SFRPl）和分泌型卷曲相关蛋白2（SFRP2）在肾细胞癌组织中的表达及其意义。方法：采用免疫组织化学方法对55例肾细胞癌组织及15例癌旁正常肾组织的SFRPl、SFRP2表达情况进行检测,初步探讨两者与肾细胞癌生物学特性的关系。结果：SFRPI和SFRP2在癌旁肾组织中较肾细胞癌组织明显增高（P〈0．01）。SFRPl和SFRP2阳性表达率在不同组织学类型的肾细胞癌中差异无统计学意义（P〉0．05）。SFRPl和SFRP2表达主要与病理分期、肿瘤细胞分级有关（P〈0．05）,而与患者年龄、性别、肿瘤直径及临床表现无关（P〉O．05）。在肾细胞癌中,SFRPl与SFRP2表达具有相关性。应用Spearman相关检验分析得出：SFRPl表达与SFRP2表达呈正相关（r=0．392,P=0．003）。结论：wnt信号通路拮抗剂SFRPl和SFRP2在RCC中表达下调或减弱,SFRPl、SFRP2可能为预防RCC及RCC早期诊断和预后评估提供新思路。     

Effects of sclerostin antibody on healing of a non‐critical size femoral bone defect

Sclerostin is a glycoprotein secreted by osteocytes and inhibits osteoblastogenesis via inhibition of Wnt signaling. We hypothesized that sclerostin antibody (Scl‐AbIII) would accelerate the healing of a murine femoral non‐critical size bone defect model. A unilateral and unicortical 0.8 mm‐sized drill hole was made in the proximal femoral shaft of adult female nude mice. One group of mice received subcutaneous injections of Scl‐AbIII and a second group received vehicle only. Reporter MC3T3 osteoprogenitor cells were injected via the tail vein 3 days after surgery to monitor systemic trafficking of exogenous osteoprogenitors. Bioluminescence imaging (BLI), microcomputed tomography (microCT), micropositron emission tomography (microPET) and histological analysis were used to compare the bone healing responses to Scl‐AbIII treatment. Bone mineral density (BMD) significantly increased at the defect site after week 1, and was significantly higher in the treatment compared with the control group at all time points. This finding was also confirmed on histological analysis by increased deposition of new woven bone. MicroPET scanning showed a trend for greater activity in the control group at day 21 compared with the Scl‐AbIII group, indicating early bone maturation following treatment with Scl‐AbIII. Whereas the BLI signals derived from the injected osteoprogenitor cells showed no differences between vehicle and Scl‐AbIII treated groups, systemic migration of MC3T3 cells to the bone defect was clearly identified in both groups using immunohistochemistry. Systemic administration of Scl‐AbIII resulted in earlier healing and maturation of a non‐critical size bone defect. These findings underscore the potential use of Scl‐AbIII for treatment of complicated fractures, non‐unions, and other clinical scenarios. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:155–163, 2012     

MicroRNA-147b suppresses the proliferation and invasion of non-small-cell lung cancer cells through downregulation of Wnt/β-catenin signalling via targeting of RPS15A

Deregulation of microRNAs (miRNAs) leads to malignant growth and aggressive invasion during cancer occurrence and progression. miR-147b has emerged as one of the cancer-related miRNAs that are dysregulated in multiple cancers. Yet, the relevance of miR-147b in non-small-cell lung cancer (NSCLC) remains unclear. In the present study, we aimed to report the biological function and signalling pathways mediated by miR-147b in NSCLC. Our results demonstrate that miR-147b expression is significantly downregulated in NSCLC tissues and cell lines. Overexpression of miR-147b decreased the proliferative ability, colony-forming capability, and invasive potential of NSCLC cells. Notably, our study identified ribosomal protein S15A (RPS15A), an oncogene in NSCLC, as a target gene of miR-147b. Our results showed that miR-147b negatively modulates RPS15A expression in NSCLC cells. An inverse correlation between miR-147b and RPS15A was evidenced in NSCLC specimens. Moreover, miR-147b overexpression downregulated the activation of Wnt/β-catenin signalling via targeting of RPS15A. Overexpression of RPS15A partially reversed the miR-147b-mediated antitumour effect in NSCLC cells. Collectively, these findings reveal that miR-147b restricts the proliferation and invasion of NSCLC cells by inhibiting RPS15A-induced Wnt/β-catenin signalling and suggest that the miR-147b/RPS15A/Wnt/β-catenin axis is an important regulatory mechanism for malignant progression of NSCLC.     

MicroRNA-367-3p overexpression represses the proliferation and invasion of cervical cancer cells through downregulation of SPAG5-mediated Wnt/β-catenin signalling

MicroRNA-367-3p (miR-367-3p) has been previously reported as a cancer-related miRNA that is dysregulated in various cancer types and functions either as an oncogenic or as tumour suppressive miRNA. However, whether miR-367-3p is dysregulated in cervical cancer and, further, whether it contributes to the development and progression of the disease remains unknown. Here, our results demonstrated that miR-367-3p expression was markedly decreased in both cervical cancer tissues and cell lines compared with corresponding controls. In vitro experiments revealed that miR-367-3p overexpression repressed the proliferation and invasion of cervical cancer cells. Notably, sperm-associated antigen 5 (SPAG5) was identified as a target gene of miR-367-3p. Moreover, decreased expression of miR-367-3p was correlated with high expression of SPAG5 in cervical cancer tissue specimens. SPAG5 inhibition or miR-367-3p overexpression significantly downregulated Wnt/β-catenin signalling in cervical cancer cells. However, the antitumour effect mediated by miR-367-3p overexpression was partially reversed by SPAG5 overexpression. Overall, these findings demonstrate that miR-367-3p overexpression restricts the proliferation and invasion of cervical cancer cells through targeting SPAG5 to downregulate Wnt/β-catenin signalling, suggesting a mechanism for the tumour suppressive function of miR-367-3p in cervical cancer. Our study highlights the involvement of miR-367-3p/SPAG5/Wnt/β-catenin signalling axis in regulating the malignant progression of cervical cancer.     

Propofol inhibits biological functions of leukaemia stem and differentiated cells through suppressing Wnt/β-catenin and Akt/mTOR

The biological roles of intravenous anaesthetic propofol in cancer have been shown by various studies using cancer cell lines that represent differentiated cancer cells. However, the activities of propofol in cancer stem cells have not been elucidated. In this work, we examined the effects and mechanisms of propofol on acute myeloid leukaemia (AML) differentiated and CD34⁺CD38⁻ stem cells. We found that propofol inhibited growth, differentiation and self-renewal capabilities of AML stem cells regardless of cellular origin and genetic profiling. In addition, propofol inhibited the growth of AML differentiated cells. Propofol significantly induced apoptosis of AML differentiated but not CD34⁺CD38⁻ stem cells. We further found that propofol significantly augmented the efficacy of AML standard therapeutic drugs. Consistent with the previous findings, we showed that propofol suppressed the Akt/mTOR pathway in AML cells. We also found that propofol inhibited pathways important for stem cell maintenance and self-renewal, such as Wnt/β-catenin. Overexpression of constitutively active Akt partially reversed the inhibitory effects of propofol in AML differentiated cells. Stabilization of β-catenin using genetic and pharmacological approaches also partially rescued the inhibitory effects of propofol in AML differentiated and stem cells. Our work shows that propofol targets leukaemia cells at all stages of development, in a cell type-specific manner. Inhibition of both Akt/mTOR and Wnt/β-catenin is required for the action of propofol in AML. Our findings also highlight the activities of propofol on cancer stem cells.