LncRNA LINC00460 promotes tumor growth of human lung adenocarcinoma by targeting miR-302c-5p/FOXA1 axis.

Accumulating evidence has shown that long non-coding RNAs (lncRNAs) had malfunctioning roles in the development of human cancers, especially lung adenocarcinoma (LC). In the present study, we aimed to investigate the role and potential mechanism of lncRNA long intergenic non-protein coding RNA 460 (LINC00460) in LC progression using human tissues and cell lines. We observed that LINC00460 was increased in lung adenocarcinoma tissues and cells in comparison to their corresponding controls. Moreover, overexpression of LINC00460 indicated the poor prognosis of lung adenocarcinoma patients. In addition, silencing LINC00460 was able to suppress lung adenocarcinoma cell growth in vitro and in vivo. Rescue assay confirmed that LINC00460 contributed to lung adenocarcinoma progression by regulating miR-302c-5p/FOXA1 signal pathway. In conclusion, LINC00460 promotes LC progression by competitively binding miR-302c-5p and regulating FOXA1 signal pathway. Our findings reveal that LINC00460 may be a potential prognostic biomarker and a candidate target for LC therapy.

Twist mediates an aggressive phenotype in human colorectal cancer cells.

Epithelial-mesenchymal transition (EMT) is a crucial process providing cancer cells with the ability to migrate and metastasize to distant sites. Recently, EMT was shown to be associated with the cancer stem cell (CSC) phenotype and chemoresistance. Twist is a transcription factor that regulates EMT in a various cancer cells, including colorectal cancer (CRC). Our study was done to determine the role of Twist in mediating aggressive phenotype in CRC. Human CRC cell lines were transduced with a retroviral Twist construct or vector control. Migration and invasion abilities were determined in vitro using modified Boyden chamber assays. Mammosphere formation assay was performed to detect CSC characteristics. EMT and CSC markers were detected using western blotting and RT-PCR. Chemosensitivity to oxaliplatin of the transfected cells were determined by the MTT assay. Human CRC specimens were stained for Twist and P-gp expression. Twist overexpression triggered EMT and a CSC-like phenotype in human CRC cells and enhanced cell migration, invasion and mammosphere formation abilities. In addition, Twist-overexpressing CRC cells were more chemo-resistant to oxaliplatin than control cells. Furthermore, Twist over-expression increased P-gp expression in CRC cells, which is a transmembrane glycoprotein conferred multidrug-resistance phenotype to various cancer cells. Importantly, Twist and P-gp were expressed correlatively in human CRC specimens. Thus, Twist is a potential therapeutic target in metastatic CRC.

Endostar enhances the antitumor effects of radiation by affecting energy metabolism and alleviating the tumor microenvironment in a Lewis lung carcinoma mouse model.

Lung cancer is a leading cause of morbidity and mortality. Previous studies have identified that an improvement in treatment efficacy was achieved using Endostar; however, the role of Endostar in lung cancer remains poorly understood. The present study investigated whether the enhanced antitumor effects of Endostar in combination with radiation involved changes in the metabolism and microenvironment in non-small cell lung cancer. A Lewis lung carcinoma mouse model was used, including the control, Endostar (ES), radiotherapy (RT) and Endostar plus radiotherapy (ES + RT) groups. The tumor inhibition rates and growth were described based on changes in tumor volume. In addition, ultraviolet enzymatic analysis was performed to determine the lactate level and reverse transcription-polymerase chain reaction was used to measure the mRNA expression of lactate dehydrogenase (LDH). A Meph-3 pH meter was used to detect the ranges of tumor interstitial tissue pH, and immunohistochemical analysis was adopted to examine hypoxia within the tumor microenvironment. The tumor inhibition rate of the ES + RT group was significantly higher compared with the other three groups (P<0.05). Following treatment, the lactate levels decreased in all three treatment groups compared with the control, particularly in the ES + RT group (P<0.05). Reduced LDH expression and hypoxic fraction in the tumor microenvironment were also observed in the ES + RT group (P<0.05). Furthermore, changes from acidic to alkaline pH in the tumor microenvironment were detected in the ES + RT group. The present study suggested that Endostar is involved in the regulation of metabolism and tumor microenvironment hypoxia, which may be responsible for the enhanced antitumor effect of Endostar in combination with radiotherapy.

N-acetyltransferase 2 phenotype and risk of esophageal cancer: a meta analysis.

N-acetyltransferase 2 (NAT2) gene encodes a phase II enzyme taking part in detoxification of aromatic amines. Published studies have demonstrated that N-Acetyltransferase 2 (NAT2) phenotype is a risk factor of various cancers. Many studies have investigated the association between NAT2 phenotype and susceptibility to esophageal cancer but yielded controversial results. To derive a more precise estimation of this association, a meta-analysis was performed. Electronic databases (Pubmed/Medline, ISI Web of Science and China National Knowledge Infrastructure) in English and Chinese were searched. A total of 5 articles including 476 cases and 1,093 controls were included in this meta-analysis. Odds ratio (OR) with 95% confidence interval (95% CI) was used to evaluate intensity of associations. Pooling studies together, NAT2 slow acetylator phenotype was a significant risk factor of esophageal squamous cell cancer (OR=1.35, 95% CI=1.03-1.77, n=5 studies) but not esophageal adenocarcinoma (OR=0.97, 95% CI=0.47-2.04, n=2 studies). There was a significant association between NAT2 acetylator phenotypes and ESCC in South Asian populations (OR=1.51, 95% CI=1.03-2.20), but not in East Asian populations (OR=1.19, 95% CI=0.80-1.77). Significant association between NAT2 acetylator phenotypes and esophageal cancer was found in population-based control subgroup (OR=1.63, 95% CI=1.07-2.50) but not in hospital-based control subgroup (OR=1.19, 95% CI=0.84-1.69). There is a significant association between NAT2 acetylator phenotype and esophageal cancer in both smokers (OR=1.681, 95% CI=1.179-2.395) and non-smokers (OR=1.614, 95% CI=1.173-2.222). In conclusion, NAT2 slow acetylator phenotype was a significant risk factor of ESCC in Asian populations.

[Inhibitive effect of human foamy virus induced IL-24 on cancer cells].

AIM: To construct replication-defective HFV-IL24 virus vector and to investigate its inhibitive effect on cancer cells after infected or transfected by this vector. METHODS: pDeltaphi-IL24 was constructed and was co-transfected with helper-plasmids into HEK 293T cells. Recombinant HFV-IL24 vector was extracted to infect HeLa cells and the inhibitive effect of IL-24 on cancer cells was examined by RT-PCR, MTT, cell counting and FCM methods. RESULTS: pDeltaphi-IL24 plasmid and HFV-IL24 particles were successfully constructed. HeLa cells exhibited obvious growth inhibition, cell cycle variation and visible apoptosis (mortality) after infected or transfected by HFV-IL24 or pDeltaphi-IL24. CONCLUSION: The results of the study provide some evidence for human foamy virus used as an effective gene transfer tool and for cancer gene therapy with HFV-IL24.

[Association of MLH1 gene 415G/C polymorphism with colorectal cancer in Chinese].

OBJECTIVE: To study the possible etiological role of MLH1 gene 415G/C polymorphism in sporadic Chinese colorectal cancer (CRC) patients. METHODS: Ninety-seven sporadic CRC patients and 138 normal controls were collected from Hubei Provincial Cancer Hospital and the People's Hospital of Wuhan University. In addition, five CRC families including 6 patients and their 19 first-degree relatives were also recruited. Genomic DNA was extracted from peripheral blood samples. Gene mutation was analyzed by PCR-RFLP. MLH1 mRNA expression in colorectal mucosa was analyzed by RT-PCR. RESULTS: The frequency of MLH1 gene CC genotype was significantly higher in sporadic CRC patients than that in controls (P=0.035, OR=5.29, 95% CI: 1.07-26.04). In the CRC families, the C allele frequency of CRC patients and their relatives was increased, compared with sporadic CRC patients and normal controls, respectively (P=0.003 and P=0.006). MLH1 mRNA expression of colorectal mucosa was similar in different genotypes. CONCLUSION: MLH1 gene 415G/C polymorphism might be a risk factor to sporadic CRC in Chinese. The mutation does not affect the MLH1 mRNA expression. For first-degree relatives from CRC families, carriers of MLH1 415C allele have a high risk to CRC.