Anjia Han

MACC1 down-regulation inhibits proliferation and tumourigenicity of nasopharyngeal carcinoma cells through Akt/β-catenin signaling pathway.

The present study was aimed at investigating the expression of metastasis-associated in colon cancer 1 (MACC1) in nasopharyngeal carcinoma (NPC), its relationship with β-catenin, Met expression and the clinicopathological features of NPC, and its roles in carcinogenesis of NPC. Our results showed that MACC1 expression was higher in NPC cells and tissues than that in normal nasopharyngeal cells and chronic inflammation of the nasopharynx tissues, respectively. MACC1 expression was closely related to the clinical stage (p = 0.005) and the N classification (p<0.05) of NPC. Significant correlations between MACC1 expression and Met expression (p = 0.003), MACC1 expression and β-catenin abnormal expression (p = 0.033) were found in NPC tissues. MACC1 knockdown dramatically inhibited cellular proliferation, migration, invasion, and colony formation, but induced apoptosis in NPC cells compared with the control group. Furthermore, MACC1 down-regulation inhibited phosphorylated-Akt (Ser473) and β-catenin expression in NPC cells, but phosphorylated-Erk1/2 expression was not altered. Further study showed that phosphotidylinsitol-3-kinase inhibitor downregulated β-catenin and Met expression in NPC cells. There was a significant relationship between MACC1 expression and phosphorylated-Akt expression (p = 0.03), β-catenin abnormal expression and phosphorylated-Akt expression (p = 0.012) in NPC tissue, respectively. In addition, Epstein Barr virus-encoded oncogene latent membrane protein 1 upregulated MACC1 expression in NPC cells. Our results firstly suggest that MACC1 plays an important role in carcinogenesis of NPC through Akt/β-catenin signaling pathway. Targeting MACC1 may be a novel therapeutic strategy for NPC.

Astrocyte elevated gene‐1 interacts with β‐catenin and increases migration and invasion of colorectal carcinoma

To investigate the astrocyte elevated gene‐1 (AEG‐1) expression and its relationship with the clinicopathological features of colorectal carcinoma (CRC) and β‐catenin signaling pathway. Real‐time PCR, Western blot, immunohistochemistry, and immunofluorescence staining were performed to detect AEG‐1 expression in CRC cell lines, 8 pairs of fresh CRC and adjacent nontumor tissues (ANT), 120 pairs of paraffin‐embedded CRC specimens and ANT tissues, and 60 samples of lymph node metastatic CRC tissues. Scratch wound assay and transwell matrix penetration assay were performed to determine migration and invasion of SW480 cell lines with stable AEG‐1 overexpression or SW620 cell lines with AEG‐1 knockdown. AEG‐1 expression was upregulated in CRC cell lines and tissues compared with ANT. Furthermore, AEG‐1 expression level significantly correlated with UICC stage, and the N classification. AEG‐1 overexpression significantly enhanced migration and invasion of SW480 cell lines. However, AEG‐1 knockdown suppressed migration and invasion of SW620 cell lines. Meanwhile, there was a positive correlation between AEG‐1 high expression and β‐catenin nuclear expression in CRC. AEG‐1 overexpression increased nuclear β‐catenin accumulation in CRC cell lines. AEG‐1 knockdown decreased nuclear β‐catenin accumulation in CRC cell lines. Moreover, we firstly found that AEG‐1 interacted with β‐catenin in SW480 cell lines. Our results for the first time showed that AEG‐1 interacted with β‐catenin in CRC cells and AEG‐1 expression was closely associated with progression of CRC. AEG‐1 might be a potential therapeutic target in CRC.

Clinical and biological significance of miR-378a-3p and miR-378a-5p in colorectal cancer

To investigate miR-378a-3p and miR-378a-5p expression and their relationships with the clinicopathological features of colorectal cancer (CRC). Our results showed that miR-378a-3p and miR-378a-5p expression were dramatically lower in CRC cell lines and tissues than that in adjacent normal colorectal mucosal tissues, respectively. MiR-378a-3p and miR-378a-5p expression were significantly associated with histological differentiation and TNM stage, respectively. CRC patients with low miR-378a-3p and miR-378a-5p expression had a significantly shorter survival time than those patients with high miR-378a-3p and miR-378a-5p expression (p<0.001, p<0.001), respectively. Univariate and multivariable Cox regression analysis showed that tumour size, TNM stage, miR-378a-3p expression and miR-378a-5p expression were independent prognostic factors for CRC patients. Ectopic miR-378a-3p or miR-378a-5p expression inhibited cellular proliferation and colony formation, induced apoptosis and G1-phase cell cycle arrest in CRC cells, but had no effect on migration and invasion of CRC cells. Furthermore, miR-378a-3p over-expression or down-regulation could inhibit or enhance insulin-like growth factor 1 receptor (IGF1R) expression in CRC cells. There was a significantly negative correlation between IGF1R protein expression and miR-378a-3p expression in CRC tissues. MiR-378a-3p over-expression or down-regulation suppressed or enhanced phosphorylated-ERK1/2 protein level, but had no effect on phosphorylated-Akt protein level. In conclusion, miR-378a-3p and miR-378a-5p expression might play an important role as tumour suppressor gene in the initial stage of carcinogenesis of CRC.

Clinical and biological significance of hepatoma‐derived growth factor in Ewing's sarcoma

We sought to investigate the clinicopathological significance and biological function of hepatoma‐derived growth factor (HDGF) in Ewings sarcoma. Our results showed that HDGF expression is up‐regulated in Ewings sarcoma. Nuclear HDGF expression is significantly associated with tumour volume (p < 0.001), metastases at diagnosis (p < 0.001), low overall survival rate (p < 0.001) and low disease‐free survival rate (p < 0.001). HDGF knock‐down results in significant reduction of Ewings sarcoma cell growth, proliferation and enhances tumourigenesis, both in vitro and in vivo. Meanwhile, HDGF knock‐down causes cell cycle arrest and enhanced sensitization to serum starvation‐induced apoptosis. Furthermore, recombinant HDGF promotes proliferation and colony formation of Ewings sarcoma cells. Ninety‐eight candidate HDGF downstream genes were identified in Ewings sarcoma cells using cDNA microarray analysis. In addition, we found that HDGF knock‐down inhibited FLI1 expression in Ewings sarcoma cells at the mRNA and protein levels. Our findings suggest that HDGF exhibits oncogenic properties and may be a novel prognostic factor in Ewings sarcoma. Targeting HDGF might be a potential therapeutic strategy for Ewings sarcoma. Copyright

EBV-encoded LMP1 increases nuclear β-catenin accumulation and its transcriptional activity in nasopharyngeal carcinoma

This paper aimed to study whether Epstein–Barr virus-encoded latent membrane protein 1 (LMP1) regulates β-catenin signaling pathway in nasopharyngeal carcinoma (NPC). Western blotting, immunofluorescence, luciferase reporter assay, co-immunoprecipitation assay, and immunohistochemistry staining were used. LMP1 increased β-catenin transcriptional activity in NPC cell lines. The upregulation of β-catenin transcriptional activity induced by LMP1 was much higher in poorly differentiated NPC cell line CNE2 than that in well-differentiated NPC cell line CNE1. Immunofluorescence staining and Western blotting also showed that LMP1 increased nuclear β-catenin accumulation in NPC cell lines. Moreover, LMP1 expression was closely related to abnormal β-catenin expression in NPC tissues by immunohistochemistry. LMP1 may be involved in nasopharyngeal carcinogenesis via β-catenin signaling pathway.

Suppression of nasopharyngeal carcinoma cell by targeting β-catenin signaling pathway

AIM To investigate the role of β-catenin in pathogenesis of nasopharyngeal carcinoma (NPC). METHODS Cellular proliferation, apoptosis, matrix penetration assay, and western blotting were employed to determine cell biological changes in NPC cell lines transfected with β-catenin siRNA. Immunohistochemistry staining was used to detect β-catenin and Ki-67 expression in NPC tissue. RESULTS β-Catenin was upregulated in NPC cell lines and tissues compared with chronic nasopharyngitis tissue. β-Catenin knockdown dramatically inhibited cellular growth, migration and invasion, but induced apoptosis of NPC cells. Further study showed that downstream genes of β-catenin signaling pathway including cyclin D1, c-Myc, MMP2 and MMP9 expression were suppressed in NPC cell lines transfected with β-catenin siRNA. CONCLUSION Targeting β-catenin signaling pathway may be a noval strategy for NPC therapy.

Suppression of retinoid X receptor alpha and aberrant β-catenin expression significantly associates with progression of colorectal carcinoma

To investigate retinoid X receptor alpha (RXRα) and β-catenin expression and their relationship with the clinicopathological features of colorectal carcinoma (CRC). Real-time PCR and western blot analyses revealed that β-catenin and RXRα expression at both mRNA and protein levels in four pairs of fresh CRC and adjacent non-tumour tissues (ANT) dramatically was increased and decreased in CRC compared with ANT, respectively. Furthermore, RXRα expression at both mRNA and protein levels was downregulated in higher histological grade CRC. Immunohistochemistry staining in 120 cases of CRC and 60 cases of lymph node metastatic carcinoma of CRC showed that RXRα expression was significantly suppressed in CRC compared with ANT (P<0.001) and low expression of RXRα in CRC was significantly associated with histological grade (P<0.001), TNM stage (P=0.022) and N classification (P=0.002). The aberrant (accumulated cytoplasm or/and nuclei) expression of β-catenin was higher in CRC than that in ANT (P<0.001) and associated with histological grade (P=0.001) and N classification (P=0.002). Moreover, there was a close relationship between low RXRα expression and aberrant β-catenin expression in CRC (P=0.032). Taken together with our previous study, aberrant β-catenin expression upregulated by suppression of RXRα may play a crucial role in pathogenesis and progression of CRC.

Clinicopathological features of inflammatory pseudotumour‐like follicular dendritic cell tumour of the abdomen

Inflammatory pseudotumour‐like follicular dendritic cell (FDC) tumour is an extremely rare neoplasm. Herein, we report 10 cases of inflammatory pseudotumour‐like FDC tumours in the abdomen and analyse their clinicopathological features.

p53 and hepatoma-derived growth factor expression and their clinicopathological association with Ewing family tumour

Purpose To investigate p53 and hepatoma-derived growth factor (HDGF) expression and their association with clinicopathological features of Ewing family tumour (EFT). Experimental design A total of 108 cases of EFT were retrospectively analysed. p53 and HDGF expression were detected using immunohistochemistry, and the relationships between p53 expression and HDGF expression and clinicopathological features of EFT were analysed. Kaplan–Meier curves were applied to estimate overall survival, log-rank test was used to assess prognostic relevance of p53 expression with overall survival and Cox regression model was performed to evaluate HRs. Results p53 expression and high HDGF expression was found in 17 (15.7%) and 55 (50.9%) patients, respectively. p53 expression was significantly associated with metastatic stage at initial diagnosis (p=0.007) and tumour venous/nerve invasion (p=0.023). A significant positive correlation was found between p53 expression and HDGF expression in EFT (p=0.022). p53 expression was an independent prognostic factor for overall survival of patients with EFT (p<0.001). Patients with p53-positive/high HDGF expression had a significantly shorter overall survival than those with p53-positive/low HDGF expression or p53-negative/high HDGF expression or p53-negative/low HDGF expression. We first constructed a novel molecular staging system by combining p53 expression and HDGF expression, which significantly improved prognostic stratification for patients with EFT. Conclusions p53 expression was an independent prognostic factor for patients with EFT. Combining p53 expression and HDGF expression significantly improved prognostic stratification for patients with EFT.

Blastic plasmacytoid dendritic cell neoplasm with EWSR1 gene rearrangement

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare form of haematologic neoplasm, which was previously referred to as blastic natural killer-cell lymphoma, agranular CD4 natural killer cell leukaemia or agranular CD4/CD56 haematodermic neoplasm. It1 has recently been recognised as a distinct entity and a rare subgroup of acute myeloid leukaemia (AML) and a related precursor neoplasm in WHO classification of tumours of haematopoietic and lymphoid tissues (2008). Ewing sarcoma breakpoint region 1(EWSR1) has a large number of fusion partners, mainly associated with the pathogenesis of Ewing sarcoma family tumours. Herein, we first reported one BPDCN case that showed positive EWSR1 gene rearrangement. The patient was a 5-year-old girl. She complained of painless purple skin papules for 6 months. The lesion increased to 5 cm×4 cm in size after 3 months without involvement of lymph node or other organs. The examination of peripheral blood and bone marrow revealed normal findings. Microscopically, the …