Effects of miR-152 on Cell Growth Inhibition, Motility Suppression and Apoptosis Induction in Hepatocellular Carcinoma Cells

Dang, Yi-Wu,Zeng, Jing,He, Rong-Quan,Rong, Min-Hua,Luo, Dian-Zhong,Chen, Gang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

Background: miR-152 is involved in the genesis and development of several malignancies. However, its role in HCC has not been fully clarified. The aim of this study was to investigate the clinicopathological significance of miR-152 and its effect on the malignant phenotype of HCC cells. Methods: miR-152 expression was detected using real-time quantitative RT-PCR in 89 pairs of HCC formalin-fixed paraffin-embedded and their adjacent tissues. Functionally, in vitro effects and mechanisms of action of miR-152 on proliferation, viability, caspase activity, apoptosis and motility were explored in HepG2, HepB3 and SNU449 cells, as assessed by spectrophotometry, fluorimetry, fluorescence microscopy, wound-healing and Western blotting, respectively. Results: miR-152 expression in HCC was downregulated remarkably compared to that in adjacent hepatic tissues. miR-152 levels in groups of advanced clinical stage, larger tumor size and positive HBV infection, were significantly lower than in other groups. A miR-152 mimic could suppress cell growth, inhibit cell motility and increase caspase activity and apoptosis in HCC cell lines. Furthermore, Western blotting showed that the miR-152 mimic downregulated Wnt-1, DNMT1, ERK1/2, AKT and TNFRS6B signaling. Intriguingly, inverse correlation of TNFRF6B and miR-152 expression was found in HCC and bioinformatics confirmed that TNFRF6B might be a target of miR-152. Conclusions: Underexpression of miR-152 plays a vital role in hepatocarcinogenesis and lack of miR-152 is related to the progression of HCC through deregulation of cell proliferation, motility and apoptosis. miR-152 may act as a tumor suppressor miRNA by also targeting TNFRSF6B and is therefore a potential candidate biomarker for HCC diagnosis, prognosis and molecular therapy.

Nomogram for predicting overall survival in children with neuroblastoma based on SEER database

Song-Wu Liang,Gang Chen,Yi-Ge Luo,Peng Chen,Jin-Han Gu,Qiong-Qian Xu,Yi-Wu Dang,Li-Ting Qin,Hui-Ping Lu,Wen-Ting Huang,Zhi-Guang Huang,Li Gao,Jia-Bo Chen 대한외과학회 2020 Annals of Surgical Treatment and Research(ASRT) Vol.99 No.2

Purpose: This study was performed to establish and validate a nomogram for predicting the overall survival in children with neuroblastoma. Methods: The latest clinical data of neuroblastoma in Surveillance, Epidemiology, and End Results (SEER) database was extracted from 2000 to 2016. The cases included were randomly divided into training and validation cohorts. The survival curves were drawn with a Kaplan-Meier estimator to investigate the influences of certain single factors on overall survival. Also, least absolute shrinkage and selection operator regression was applied to further select the prognostic variables for neuroblastoma. Additionally, receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the accuracy of the nomogram. Results: In total, 1,262 patients were collected and 8 independent prognostic factors were achieved, including patients’ age, sex, race, tumor grade, radiotherapy, chemotherapy, tumor site, and tumor size. Then we constructed a nomogram by using the data of the training cohort with 886 cases. Subsequently, the nomogram was validated internally and externally with 886 and 376 cases, respectively. The internal validation revealed that the area under the curves (AUC) of ROC curves of 1-, 3-, and 5-year overall survival were 0.69, 0.78, and 0.81, respectively. Accordingly, the external validation also showed that the AUC of 1-, 3-, and 5-year overall survival were all ≥0.69. Both methods of validation demonstrated that the predictive calibration curves were consistent with standard curves. Conclusion: The nomogram possess the potential to be a new tool in predicting the survival rate of neuroblastoma patients.

Overexpression and Clinicopathological Contribution of DcR3 in Bladder Urothelial Carcinoma Tissues

Jiang, Yi-Qiang,Zhong, Teng-Fei,Dang, Yi-Wu,Zou, Ling-Song,Yang, Liu,Yang, Xia,Chen, Gang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

Background: To explore the expression of DcR3 protein and its clinicopathological significance in bladder urothelial carcinomas (BUC). Materials and Methods: Immunohistochemistry was performed to detect the expression of DcR3, caspase-3, Bcl-2, VEGF, Ki-67, PCNA and P53 in 166 BUC and 56 normal bladder tissues. Western blotting was used to detect the expression of DcR3 in the supernatants of cultured BUC cells. Results: Overexpression of DcR3 was found in BUC tissues and cell lines, with significant elevation as compared to normal bladder tissues (p<0.0001). Higher DcR3 expression was related to the status of invasion, lymph node metastasis and recurrence. Furthermore, DcR3 expression was negatively correlated with caspase-3 and positively associated with Bcl-2, VEGF, Ki-67 labeling index (LI), PCNA LI and P53 (all p<0.0001), respectively. Conclusions: DcR3 may play a crucial role as an oncogene in tumorigenesis, deterioration and progress of BUC via influencing related pathways of apoptosis, proliferation and angiogenesis. The detection of DcR3 protein in the formalinfixed and paraffin-embedded samples could assist to predict in prognosis of BUC patients.

Expression of Tumor Necrosis Factor Receptor-associated Factor 6 in Lung Cancer Tissues

Zhang, Xiu-Ling,Dang, Yi-Wu,Li, Ping,Rong, Min-Hua,Hou, Xin-Xi,Luo, Dian-Zhong,Chen, Gang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Background: Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) has been reported to be associated with the development of various cancers. However, the role of TRAF6 in lung cancer remains unclear. Objective: To explore the expression and clinicopathological significance of TRAF6 protein in lung cancer tissues. Materials and Methods: Three hundred and sixty-five lung cancer samples and thirty normal lung tissues were constructed into 3 microarrays. The expression of TRAF6 protein was determined using immunohistochemistry (IHC). Furthermore, correlations between the expression of TRAF6 and clinicopathological parameters were investigated. Results: The expression of TRAF6 in total lung cancer tissues (365 cases), as well as in small cell lung cancer (SCLC, 26 cases) and non-small cell lung cancer (NSCLC, 339 cases) was significantly higher compared with that in normal lung tissues. The ROC curve showed that the area under curve of TRAF6 was 0.663 (95%CI 0.570~0.756) for lung cancer. The diagnostic sensitivity and specificity of TRAF6 were 52.6% and 80%, respectively. In addition, the expression of TRAF6 was correlated with clinical TNM stage, tumor size and lymph node metastasis in all lung cancers. Consistent correlations were also observed for NSCLCs. Conclusions: TRAF6 might be an oncogene and the expression of TRAF6 protein is related to the progression of lung cancer. Thus, TRAF6 might become a target for diagnosis and gene therapy for lung cancer patients.

Expression and Prognostic Significance of lncRNA MALAT1 in Pancreatic Cancer Tissues

Liu, Jiang-Hua,Chen, Gang,Dang, Yi-Wu,Li, Chun-Jun,Luo, Dian-Zhong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Background: Long non-coding RNAs (lncRNAs) have been recently observed in various human cancers. However, the role of lncRNAs in pancreatic duct adenocarcinoma (PDAC) remains unclarified. The aim of this study was to detect the expression of lncRNA MALAT1 in PDAC formalin-fixed, paraffin embedded (FFPE) tissues and to investigate the clinical significance of the MALAT1 level. Methods: The expression of MALAT1 was examined in 45 PDAC and 25 adjacent non-cancerous FFPE tissues, as well as in five PDAC cell lines and a normal pancreatic epithelium cell line HPDE6c-7, using qRT-PCR. The relationship between MALAT1 level and clinicopathological parameters of PDAC was analyzed with the Kaplan-Meier method and Cox proportional hazards model. Results: The relative level of MALAT1 was significantly higher in PDAC compared to the adjacent normal pancreatic tissues (p=0.009). When comparing the MALAT1 level in the cultured cell lines, remarkably higher expression of MALAT1 was found in aspc-1 PDAC cells compared with the immortal pancreatic duct epithelial cell line HPDE6c-7 (q=7.573, p<0.05). Furthermore, MALAT1 expression level showed significant correlation with tumor size (r=0.35, p=0.018), tumor stage (r=0.439, p=0.003) and depth of invasion (r=0.334, p=0.025). Kaplan-Meier analysis revealed that patients with higher MALAT1 expression had a poorer disease free survival (p=0.043). Additionally, multivariate analysis indicated that overexpression of MALAT1, as well as the tumor location and nerve invasion, was an independent predictor of disease-specific survival of PDAC. Conclusion: MALAT1 might be considered as a potential prognostic indicator and may be a target for diagnosis and gene therapy for PDAC.

Upregulation and Clinicopathological Significance of Long Non-coding NEAT1 RNA in NSCLC Tissues

Pan, Lin-Jiang,Zhong, Teng-Fei,Tang, Rui-Xue,Li, Ping,Dang, Yi-Wu,Huang, Su-Ning,Chen, Gang Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7

Background: Recent reports have shown that nuclear enriched abundant transcript 1 (NEAT1), a long noncoding RNA (lncRNA), contributes to the precise control of gene expression and is related to several human malignancies. However, limited data are available on the expression and function of NEAT1 in lung cancer. The major objective of the current study was to profile the expression and clinicopathological significance of NEAT1 in non-small cell lung cancers (NSCLCs). Materials and Methods: NEAT1 expression in 125 NSCLC cases and paired adjacent non-cancer tissues was assessed by real-time quantitative reverse transcription-PCR (qRT-PCR). Relationships between NEAT1 and clinicopathological factors were also investigated. Results: The relative level of NEAT1 was $6.98{\pm}3.74$ in NSCLC tissues, significantly elevated as compared to that of the adjacent non-cancer lung tissues ($4.83{\pm}2.98$, p<0.001). The area under curve (AUC) of high expression of NEAT1 to diagnose NSCLC was 0.684 (95% CI: 0.619~0.750, p<0.001). NEAT1 expression was positively correlated with patient age (r=-2.007, p=0.047), lymphatic metastasis (r=-2.731, p=0.007), vascular invasion (r=-3.617, p=0.001) and clinical TNM stage (r=-4.134, p<0.001). Conclusions: This study indicates that NEAT1 might be associated with oncogenesis and progression in NSCLC, and suggests application in molecular targeted therapy.