SH3PXD2A-AS1/miR-330-5p/UBA2 ceRNA network mediates the progression of colorectal cancer through regulating the activity of the Wnt/ß-catenin signaling pathway.

Long non-coding RNAs have important roles in the occurrence and progression of various cancers. However, the molecular mechanism of lncRNAs in colorectal cancer (CRC) is not well illustrated. Thus, we used bioinformatics methods to find potential lncRNAs associated with CRC progression, and chose SH3PXD2A-AS1 as a candidate for further analysis. The roles of SH3PXD2A-AS1 in CRC cells were determined by CCK-8, transwell invasion, wound healing and flow cytometry assays. Besides, we established the CRC tumor models in nude mice to study the effect of SH3PXD2A-AS1 on the tumor growth. Based on the ceRNA hypothesis, we used miRDB and miRTarBase websites to identify the SH3PXD2A-AS1-related ceRNA regulatory network, and measured the roles of this network in CRC cells. The results revealed that the expression profiles of SH3PXD2A-AS1 from GEO and TCGA databases showed an aberrant high level in CRC tissues compared with colorectal normal tissues. SH3PXD2A-AS1 over-expression was also found in CRC cells. SH3PXD2A-AS1 knockdown inhibited the CRC cellular proliferation, invasion and migration but induced apoptosis. Besides, SH3PXD2A-AS1 knockdown also suppressed the growth of CRC tumors. Furthermore, SH3PXD2A-AS1 could function as a ceRNA of miR-330-5p. Additionally, UBA2 was proved to be a target gene of miR-330-5p. Moreover, SH3PXD2A-AS1 knockdown downregulated UBA2 expression through sponging miR-330-5p to inactivate the Wnt/ß-catenin signaling pathway, thereby inhibiting the cell growth and promoting apoptosis. Therefore, the SH3PXD2A-AS1/miR-330-5p/UBA2 network could regulate the progression of CRC through the Wnt/ß-catenin pathway. These findings offer new sights for understanding the pathogenesis of CRC and provide potential biomarkers for CRC treatment.

Genetic variability of genes in NER pathway influences the treatment outcome of gastric cancer.

We performed a study to investigate the role of ERCC1, ERCC2, ERCC5, XPA and XPC polymorphisms from perspective of the whole NER pathway in the prognosis of gastric cancer. A total of 410 gastric cancer patients were recruited between January 2010 and December 2011. Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to analyze genotypes of ERCC1 rs11615 and rs3212986, ERCC2 rs13181 and s1799793, ERCC5 rs17655, XPA rs1800975 and XPC rs2228001. Our study found that carriers of ERCC1 rs3212986 TT genotype showed significantly favorable survival than wide-type GG genotype in multivariate analysis (OR=6.38, 95% CI=2.54-19.03), and patients with variant CC genotype of ERCC2 rs13181 exhibited better response to chemotherapy than those with AA genotype (OR=2.21, 95% CI=1.17-4.25). By Cox proportional hazards model, patients with variant TT genotype of ERCC1 rs3212986 exhibited longer PFS and OS than those who had GG genotype (for PFS, HR=0.37, 95% CI=0.17-0.75; for OS, HR=0.36, 95% CI=0.13-0.87). For ERCC2 rs13181 polymorphism, carriers with CC genotype demonstrated significantly increased hazards of progression of disease and death in multivariate model (for PFS, HR=0.48, 95% CI=0.26-0.88; for OS, HR=0.44, 95% CI=0.20-0.91). In conclusion, our finding suggests that ERCC1 rs3212986 and ERCC2 rs13181 gene polymorphism could influence the response to chemotherapy and clinical outcome of gastric cancer.

Different expression patterns of CEACAM1 and its impacts on angiogenesis in gastric nonneoplastic and neoplastic lesions.

OBJECTIVE: This study was designed to investigate the expression patterns of CEACAM1 and its relationship with angiogenesis in nonneoplastic and neoplastic gastric lesions. METHODS: CEACAM1 and TGF-ß expression was detected by immunohistochemical staining and dual-labeling immunohistochemical staining in neoplastic and nonneoplastic lesions. MVD-CD31 and MVD-CD105 were counted in CEACAM1-positive areas by dual-labeling immunohistochemistry. RESULTS: There was no expression of CEACAM1 in normal gastric mucosa. In IM and GIN, CEACAM1 was mainly expressed with membranous pattern. CEACAM1 was expressed with membranous pattern in well-differentiated adenocarcinoma, with cytoplasmic pattern in poorly differentiated adenocarcinoma, and with cytoplasmic and membranous pattern mixed together in intermediately adenocarcinoma. The expression patterns of CEACAM1 showed a significant difference (P < 0.05) in nonneoplastic and neoplastic lesions. Coexpression of CEACAM1 and TGF-ß was elevated and significantly different from nonneoplastic to neoplastic lesions (P < 0.05). Moreover, CEACAM1 and TGF-ß coexpression were related to carcinoma progression (r = 0.35; P < 0.05). MVD-CD31 and MVD-CD105 showed significant differences from nonneoplastic to neoplastic lesions (P < 0.05). CONCLUSIONS: CEACAM1 has different expression patterns in nonneoplastic and neoplastic lesions. The coexpression of CEACAM1 and TGF-ß increased from nonneoplastic to neoplastic lesions and may be related with tumor progression via promoting tumorous angiogenesis.

Evaluation of Nrf2 and IGF-1 expression in benign, premalignant and malignant gastric lesions.

The aim of this study was to investigate the expression of Nrf2 and IGF-1 in benign, premalignant, and malignant gastric lesions, and to explore the role of Nrf2 and IGF-1 in gastric carcinoma carcinogenesis. Nrf2 and IGF-1 expression was detected in normal gastric mucosa, hyperplastic polyp, intraepithelial neoplasia, and adenocarcinoma by immunohistochemistry. There was no expression of Nrf2 and IGF-1 in normal gastric mucous membrane. With the elevation of Nrf2, IGF-1 expression, their co-expressions were highly elevated from benign proliferative lesions to malignant lesions. There were significant differences between hyperplastic polyps, intraepithelial neoplasias, and adenocarcinoma (hyperplastic polys vs. intraepithelial neoplasia: P=0.012; hyperplastic polyps vs. adenocarcinoma: P=0.023; and intraepithelial neoplasia vs. adenocarcinoma: P=0.027; hyperplastic polyps vs. adenocarcinoma: P=0.0000, respectively). Nrf2 expression and IGF-1 expression were correlated positively (r=0.337, P=0.037). The increased expression of Nrf2 and IGF-1 may be related to gastric carcinogenesis. Elevated Nrf2 and IGF-1 may play important roles in promoting tumor progression.

Elevated expression of SOX9 is related with the progression of gastric carcinoma.

To investigate the SOX9 expression and its effects on promoting invasion and metastasis in the primary gastric adenocarcinomas. One hundred and eighty six patients with primary gastric adenocarcinomas who underwent surgery between 2002 and 2006 were classified as low, intermediate, and high SOX9 expression groups by immunohistochemistry (IHC). Our IHC performance showed that SOX9 was lowly expressed in lower crypt of the normal epithelium adjacent to the tumor, and SOX9 expression was also observed in the intestinal metaplastic epithelium, but no SOX9 expression was detected in the surface epithelium. The stronger SOX9 expression was observed in the T3-T4 group than in the T1-T2 group, and there was a significant difference between the two groups (P < 0.0005). The SOX9 expression was correlated with the lymph node metastasis, and it showed significant between N0, N1, N2, and N3 groups (P < 0.0005). Similar to the lymph node metastasis classification, the SOX9 expression was also related to the tumor staging. From the stage Ia-Ib to stage II-IIIa and stage IIIb-IV, the SOX9 expression was elevated and the difference was significant (P < 0.0005). On the contrary, the SOX9 expression was not related to the histological classification (P > 0.05). Also the SOX9 expression showed no significance in patient age (P > 0.05). The SOX9 is overexpressed in the advanced stage of gastric carcinoma. SOX9 is related to the tumor progression though promoting invasion and metastasis, probably via enhancing the adhesion between the tumor cells and matrix or vessels which facilitates the tumor cells metastasis.

The different expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and possible roles in gastric carcinomas.

The purpose of this study was to investigate the expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and its effects on promoting angiogenesis in gastric adenocarcinomas. Paraffin wax sections of 222 patients with gastric adenocarcinomas having undergone surgery between 2001 and 2006 were classified into three histotypes: intestinal, diffuse, and mixed carcinomas following the Laurén classification. Immunohistochemistry (IHC) was used to study the distribution of CEACAM1, and double-labeling immunohistochemistry was used to observe the relationship between CEACAM1 expression and neovascularization in carcinoma areas. No CEACAM1 expression was found in normal non-metaplastic mucosa adjacent to the tumors; but in metaplastic mucosa, CEACAM1 was expressed on the apical surface. However, all of the collected gastric carcinomas expressed CEACAM1 with cytoplasmic or membranous staining. CEACAM1 was expressed mainly with a membranous pattern in the intestinal carcinomas, and with a cytoplasmic pattern in the diffuse carcinomas. There was a significant difference between the expression patterns and the histotypes (P<0.0001). CEACAM1 expression was classified as high (> or =66% positive cells) and low (<66% positive cells), and high CEACAM1 expression was associated with lymph nodes metastasis (P<0.05). High microvessel density (MVD) was observed more frequently in the tumors with membranous expression, and low MVD in the tumors with cytoplasmic staining (P<0.0001). The transformation of CEACAM1 distribution from membrane to cytoplasm is an important incident for the reverse effects on the tumorous angiogenesis, and high expression of CEACAM1 facilitates the metastasis of carcinoma cells to lymph nodes. Moreover, the different distribution of CEACAM1 in the intestinal and diffuse carcinomas indicates a different tumorigenic pathway.

[Relationship between ALDH gene polymorphism and alcoholic liver diseases].

OBJECTIVE: To study the relationship between aldehyde dehydrogenase (ALDH) gene polymorphism and alcoholic liver disease, and investigate the genetic pathogenesis of alcoholic liver disease (ALD). METHODS: PCR, restriction endonuclease and electrophoresis were used, to detect the genotypes and alleles frequencies of ALDH gene in patients in the control group, alcohol dependent group and ALD group, and each group contained 20 patients. RESULTS: The frequencies of ALDH2*1 and ALDH2*2 allele had statistic significance between control group and ALD group (x2=4.80, P<0.05), and no statistic significance between control group and alcohol dependent group. ALDH2*1/*1 was predominant in alcohol dependent group and ALD group, while ALDH2*2/*2 was not detected. CONCLUSIONS: The gene polymorphism of ALDH is close to ALD. The allele of ALDH2*2 may be a negative risk factor for the developing of ALD