LINC00152 upregulates ZEB1 expression and enhances epithelial-mesenchymal transition and oxaliplatin resistance in esophageal cancer by interacting with EZH2.

BACKGROUND: Expression of the long non-coding mRNA LINC00152 has been reported to correlate with cancer cell resistance to oxaliplatin (L-OHP). However, little is known regarding the molecular mechanism of LINC00152 in esophageal cancer (EC). Hence, we intended to characterize the role of LINC00152 in EC, with a special focus on epithelial-mesenchymal transition (EMT) and L-OHP resistance. METHODS: We collected EC tissues and identified EC cell lines with higher L-OHP resistance, and then characterized expression patterns of LINC00152, Zeste Homologue 2 (EZH2), Zinc finger e-box binding homeobox (ZEB1) and EMT-related genes using RT-qPCR and Western blot analysis. Furthermore, their functional significance was identified by gain and loss-of-function experiments. The relationship among LINC00152, EZH2 and ZEB1 was examined using RIP, RNA pull-down and ChIP assays. Additionally, resistance of EC cells to L-OHP was reflected by CCK-8 assay to detect cell viability. Animal experiments were also conducted to detect the effects of the LINC00152/EZH2/ZEB1 on EMT and L-OHP resistance. RESULTS: LINC00152, EZH2 and ZEB1 were highly expressed in EC tissues and Kyse-150/TE-1 cells. As revealed by assays in vitro and in vivo, LINC00152 positively regulated ZEB1 expression through interaction with EZH2 to enhance EMT and L-OHP resistance in EC cells. In contrast, silencing of LINC00152 contributed to attenuated EMT and drug resistance of EC cells to L-OHP. CONCLUSIONS: Our study demonstrates that LINC00152/EZH2/ZEB1 axis can regulate EMT and resistance of EC cells to L-OHP, thus presenting a potential therapeutic target for EC treatment.

LncRNA HOTAIR-mediated MTHFR methylation inhibits 5-fluorouracil sensitivity in esophageal cancer cells.

BACKGROUND: Esophageal cancer (EC) represents one of the most aggressive digestive neoplasms globally, with marked geographical variations in morbidity and mortality. Chemoprevention is a promising approach for cancer therapy, while acquired chemoresistance is a major obstacle impeding the success of 5-fluorouracil (5-FU)-based chemotherapy in EC, with the mechanisms underlying resistance not well-understood. In the present study, we focus on exploring the role of long non-coding RNA (lncRNA) HOTAIR in EC progression and sensitivity of EC cells to 5-FU. METHODS: Paired cancerous and pre-cancerous tissues surgically resected from EC patients were collected in this study. Promoter methylation of the MTHFR was assessed by methylation-specific PCR. RIP and ChIP assays were adopted to examine the interaction of DNA methyltransferases (DNMTs) with lncRNA HOTAIR and MTHFR, respectively. EC cells resistant to 5-FU were induced by step-wise continuous increasing concentrations of 5-FU. The sensitivity of EC cells to 5-FU in vivo was evaluated in nude mice treated with xenografts of EC cells followed by injection with 5-FU (i.p.). RESULTS: We found reciprocal expression patterns of lncRNA HOTAIR and MTHFR in EC tissues and human EC cells. Interference with lncRNA HOTAIR enhanced 5-FU-induced apoptosis, exhibited anti-proliferative activity, and reduced promoter methylation of the MTHFR in EC cells. Besides, overexpression of MTHFR attenuated the acquired chemoresistance induced by overexpression of lncRNA HOTAIR in EC cells. At last, enhanced chemosensitivity was observed in vivo once nude mice xenografted with lncRNA HOTAIR-depleted EC cells. CONCLUSION: Together, our study proposes that pharmacologic targeting of lncRNA HOTAIR sensitizes EC cells to 5-FU-based chemotherapy by attenuating the promoter hypermethylation of the MTHFR in EC.

[Factor analysis on trend of infant mortality and maternal health management in Henan province from 2000 to 2010].

OBJECTIVE: To understand the trends and influential factors on infant mortality in Henan province from 2000 to 2010. METHODS: Descriptive method, Cox-Stuart trend test and multiple linear regression were used to study the infant mortality trends and related influential factors in the regions with monitoring programs of Henan province, from 2000 to 2010. RESULTS: The total urban and rural infant mortality rates dropped significantly, from 30.91 per thousand, 10.05 per thousand, 33.99 per thousand in 2000 to 7.12 per thousand, 5.51 per thousand, 8.03 per thousand in 2010, respectively. The average annual rates of decrease were 13.65 percent, 5.83 percent and 13.44 percent. The downward trends were statistically significant (P < 0.05). The infant mortality rates dropped more significantly in rural areas (25.96%) than in the urban areas (4.54%). Difference between urban and rural areas reduced from 23.49% to 2.52%. Rates on factors as setting up maternal record cards, carrying on postpartum visits, hospital delivery, or under help by new midwives and low birth weight rate etc. were remarkably influencing the rate on infant mortality (F = 229.738, P = 0.004). In order, the impact of strengths on those factors showed as: hospitalized delivery rate, low birth weight rate, the rate of 'clean' delivery, setting up record cards on postpartum visits. CONCLUSION: Total provincial, urban and rural infant mortality rates all showed downward trends. The infant mortality rates dropped more significantly in rural areas than in urban areas. Difference between urban and rural areas was gradually getting small. Rates on setting up maternal record cards, carrying on postpartum visit, hospital delivery and under help by new midwives rate were important factors that significantly impacting the infant mortality rate. Work on setting up record cards and hospital delivery should be further strengthened.

[Study on AIDS incidence and death in previous paid blood-donated population, central China].

OBJECTIVE: To study incidence and death among previous paid blood-donated AIDS sufferers. METHODS: A retrospective cohort study was adopted to study incidence and death of 373 previous paid blood-donated HIV sufferers and its effect factors. RESULTS: Previous paid blood-donated HIV infection was serious and the infection rate in blood-donated crowd was 35.87% (373/1040); the mean incubation period of AIDS was 8.87 years (95% CI: 8.76 - 8.99, Kaplan-Meier method); the cumulative incidence of AIDS (10 years) was 92.23% (344/373), and the incidence of total sufferers was 11.64/100 person-year; the cumulative probability of survival of one-year, three-year, five-year AIDS sufferers was separately 94.48% (325/344), 85.76% (295/344) and 83.14% (286/344), median survival time was over 5 years; the anti-virotic treatment days (960.29 +/- 486.38), infection age (33.39 +/- 9.08) disease age (41.98 +/- 8.88) had significant effects on AIDS sufferers' survival time/survival rate (chi(2) = 61.355, P = 0.000; chi(2) = 6.555, P = 0.010; chi(2) = 3.969, P = 0.046). CONCLUSION: The survival time of previous paid blood-donated HIV cases was longer, and their survival rate was higher, remarkably higher than the UNAIDS' research findings.