Changqing Jing

Down-regulation of miR-622 in gastric cancer promotes cellular invasion and tumor metastasis by targeting ING1 gene

AIM To evaluate the biological and clinical characteristics of miR-622 in gastric cancer. METHODS We analyzed the expression of miR-622 in 57 pair matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time polymerase chain reaction. Functional analysis of miR-622 expression was assessed in vitro in gastric cancer cell lines with miR-622 precursor and inhibitor. The roles of miR-622 in tumorigenesis and tumor metastasis were analyzed using a stable miR-622 expression plasmid in nude mice. A luciferase reporter assay was used to assess the effect of miR-622 on inhibitor of growth family, member 1 (ING1) expression. RESULTS Expression of miR-622 was down-regulated in gastric cancer. MiR-622 was found involved in differentiation and lymphatic metastasis in human gastric cancer. Ectopic expression of miR-622 promoted invasion, tumorigenesis and metastasis of gastric cancer cells both in vitro and in vivo. ING1 is a direct target of miR-622. CONCLUSION These findings help clarify the molecular mechanisms involved in gastric cancer metastasis and indicate that miR-622 modulation may be a bona fide treatment of gastric cancer.

Identification of microRNAs associated with lymphangiogenesis in human gastric cancer

PurposeLymphatic metastasis is a primary cause of gastric cancer-related death, yet factors governing tumor cell lymphatic metastasis have not been fully elucidated. MicroRNAs (miRNAs) are a recently discovered class of regulatory, non-coding RNAs, some of which are involved in gastric cancer progression. However, little is known about which miRNA contributes to the lymphatic metastasis in human gastric cancer. This prompted us to find the significant miRNAs associated with lymphangiogenesis in human gastric cancer.MethodsWe screened vascular endothelial growth factor C (VEGF-C) expression in several gastric cancer cell lines as well as in the immortalized human gastric mucosal cell line GES-1, by real-time reverse transcriptase PCR (qRT-PCR). The gastric cancer cell lines MKN-45 and SGC-7901, which have commonly been cultured with human lymphatic endothelial cells (HLECs) in vitro, promoted tube formation of HLECs following transformation with a VEGF-C expression vector. Using microarrays, we identified a panel of differentially expressed miRNAs in HLECs that had been co-cultured with VEGF-C-transformed gastric cancer cells compared with non-transformed gastric cancer cells. A subset of miRNAs was further validated using qRT-PCR.ResultsWe found altered expression of miRNAs in HLECs co-cultured with lymphangiogenesis-inducing VEGF-C-transformed gastric cancer cells, with 47 up-regulated and 42 down-regulated miRNAs. These findings were confirmed by qRT-PCR of selected miRNAs. Furthermore, several miRNAs were differentially expressed in patients with positive lymphatic metastasis of the primary gastric tumor. Up-regulated miRNAs included miR-648, miR-5002-3p, miR-4754, miR-4760-5p, miR-4491, miR-4252, miR-5007-3p, and miR-647; and down-regulated miRNAs included miR-3178, miR-593-5p, miR-4485, miR-135a-3p, miR-17, miR-1469, and miR-124-5p.ConclusionsSeveral lymphangiogenesis-related miRNAs are significantly altered during lymphatic metastasis of gastric cancer.

The Diagnostic Efficacy and Biological Effects of microRNA-29b for Colon Cancer

Background: Colorectal cancer is one of the most common cancers worldwide in terms of both incidence and mortality. The associations of expressions of tissue and plasma miR-29b were not detected in this study. Methods: There are 400 healthy age- and gender-matched controls enrolled in this study in a rate of 1:2. The receiver operating characteristic curve analysis was undertaken using the expression level for miR-29b in the colorectal cancer specimens from patients with cancer and healthy controls to assess the diagnostic accuracy of both tissue and plasma miR-29b levels. Results: It was found that the expression of plasma miR-29b is associated with the tissue miR-29b. Advanced study showed that aberrant miR-29b expression in both cancer tissues and plasma is associated with the clinicopathological data of patients with colorectal cancer. Tissue miR-29b showed an AUC of 0.883, with a sensitivity of 81.6% and a specificity of 84.9%. However, the AUC for plasma miR-29b was 0.743, with a sensitivity of 61.4% and a specificity of 72.5%. The analyses of the biological effects of miR-29b for colorectal cancer showed that miR-29b could inhibit the cell viability and migration. Conclusion: In summary, our data suggest that both the tissue and the plasma miR-29b levels have some value as a diagnostic tool for colorectal cancer. Advanced biological effects were conducted to detect the potential effect on the cell viability and migration. Future investigations including larger patient populations and patients with early-stage colorectal cancer are needed to confirm the potential diagnostic value of miRNA-29b in colorectal cancer.

Expression of tumor necrosis factor α-induced protein 8 is upregulated in human gastric cancer and regulates cell proliferation, invasion and migration.

Tumor necrosis factor α-induced protein 8 (TNFAIP8) has been associated with the tumorigenicity of various types of cancer, however, the expression of TNFAIP8 and its function in gastric cancer remain to be fully elucidated. Therefore, the present study examined the expression and biological function of TNFAIP8 in gastric cancer. The expression levels of TNFAIP8 were determined in 86 gastric cancer tissue samples and adjacent normal tissues using immunohistochemistry, and in four gastric cancer cell lines and GES-1 cells using reverse transcription-quantitative polymerase chain reaction. The expression of TNFAIP8 and its association with the tumor, node, metastasis (TNM) status and lymphatic metastasis of gastric cancer was evaluated. Furthermore, the functions of decreased expression levels of TNFAIP8 were analyzed in human gastric cancer cell lines. The expression of TNFAIP8 was significantly upregulated in the gastric cancer tissues and in the gastric cancer cell lines, and its expression levels were associated with the TNM staging and lymphatic metastasis. Furthermore, decreased expression of TNFAIP8 inhibited the growth, invasion and migration of gastric cancer cells. These data provided an innovative insight suggesting the downregulation of TNFAIP8 as a meaningful approach for treating human gastric cancer and other types of cancer. In addition, the expression levels of TNFAIP8 may be considered as a biomarker of gastric cancer progression.

Semaphorin 4D and hypoxia-inducible factor-1α overexpression is related to prognosis in colorectal carcinoma

AIM To investigate semaphorin 4D (Sema4D) and hypoxia-inducible factor-1α (HIF-1α) expression in colorectal carcinoma and evaluate their clinicopathological and prognostic significance. METHODS Eighty-six curatively resected colorectal carcinoma patients at different stages of disease were randomly selected from the group of patients who underwent surgery, and none of them received preoperative radiochemotherapy. Normal proximal adjacent bowel tissue, which served as an internal control, was obtained from 52 randomly selected patients. Immunohistochemistry was performed to analyze the expression of Sema4D and the tumor angiogenesis-related protein HIF-1α in normal colorectal tissues and colorectal carcinoma tissues. The relationships between the expression and clinical characters and prognosis were analyzed. RESULTS HIF-1α and Sema4D were positively expressed in 58% and 60% of colorectal carcinoma tissues, respectively. Significantly lower expression levels were observed in normal mucosa (8% and 12%, respectively). HIF-1α and Sema4D expression was closely correlated with histological tumor type, tumor-node-metastasis (TNM) stage, and lymphatic metastasis (P<0.05), but not with age or tumor size (P>0.05). HIF-1α and Sema4D protein expression was significantly correlated with prognosis of colorectal carcinoma, as determined by Spearman rank correlation analysis (r=0.567; P<0.01). Multivariate Cox analysis revealed that only Sema4D expression played a significant role in predicting patient prognosis (P<0.05). CONCLUSION These findings suggest that HIF-1α and Sema4D expression correlates with histological tumor type, TNM stage, and lymphatic metastasis in colorectal carcinoma and that Sema4D is a prognostic indicator of colorectal carcinoma.

BI2536, a potent and selective inhibitor of polo-like kinase 1, in combination with cisplatin exerts synergistic effects on gastric cancer cells

BI2536 is a highly selective and potent inhibitor of polo-like kinase 1 (PLK1). In this study, we aimed to determine whether BI2536 and cisplatin can synergistically inhibit the malignant behavior of gastric cancer cells. For this purpose, the expression of PLK1 in gastric cancer cells was determined. The effects of BI2536, cisplatin, and the combination of BI2536 and cisplatin on gastric cancer cell viability, invasion, cell cycle arrest and apoptosis were assessed. Furthermore, the expression of cell cycle-regulated proteins was examined. Moreover, the differentially expressed proteins between the SGC-7901 and SGC-7901/DDP (cisplatin-resistant) cells, and the enriched signaling pathways were analyzed by protein pathway array following treatment with BI2536 (IC50) for 48 h. Our results revealed that PLK1 was upregulated in the SGC-7901/DDP (cisplatin-resistant) gastric cancer cells compared with the SGC-7901 cells. BI2536 enhanced the inhibitory effect of cisplatin on SGC-7901 cell viability and invasion. BI2536 induced G2/M arrest in SGC-7901 and SGC-7901/DDP cells. BI2536 promoted cisplatin-induced gastric cancer SGC-7901/DDP cell apoptosis. It also induced the differential expression of 68 proteins between the SGC-7901 and SGC-7901/DDP cells, and these differentially expressed proteins were involved in a number of cellular functions and signaling pathways, such as cell death, cell development, tumorigenesis, the cell cycle, DNA duplication/recombination/repair, cellular movement, and the Wnt/β-catenin and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK)/ribosomal S6 kinase 1 (RSK1) signaling pathways. On the whole, our findings suggest that BI2536 and cisplatin synergistically inhibit the malignant behavior of SGC-7901/DDP (cisplatin-resistant) gastric cancer cells.