Analysis of ceRNA networks and identification of potential drug targets for drug-resistant leukemia cell K562/ADR.

BACKGROUND: Drug resistance is the main obstacle in the treatment of leukemia. As a member of the competitive endogenous RNA (ceRNA) mechanism, underlying roles of lncRNA are rarely reported in drug-resistant leukemia cells. METHODS: The gene expression profiles of lncRNAs and mRNAs in doxorubicin-resistant K562/ADR and sensitive K562 cells were established by RNA sequencing (RNA-seq). Expression of differentially expressed lncRNAs (DElncRNAs) and DEmRNAs was validated by qRT-PCR. The potential biological functions of DElncRNAs targets were identified by GO and KEGG pathway enrichment analyses, and the lncRNA-miRNA-mRNA ceRNA network was further constructed. K562/ADR cells were transfected with CCDC26 and LINC01515 siRNAs to detect the mRNA levels of GLRX5 and DICER1, respectively. The cell survival rate after transfection was detected by CCK-8 assay. RESULTS: The ceRNA network was composed of 409 lncRNA-miRNA pairs and 306 miRNA-mRNA pairs based on 67 DElncRNAs, 58 DEmiRNAs and 192 DEmRNAs. Knockdown of CCDC26 and LINC01515 increased the sensitivity of K562/ADR cells to doxorubicin and significantly reduced the half-maximal inhibitory concentration (IC50) of doxorubicin. Furthermore, knockdown of GLRX5 and DICER1 increased the sensitivity of K562/ADR cells to doxorubicin and significantly reduced the IC50 of doxorubicin. CONCLUSIONS: The ceRNA regulatory networks may play important roles in drug resistance of leukemia cells. CCDC26/miR-140-5p/GLRX5 and LINC01515/miR-425-5p/DICER1 may be potential targets for drug resistance in K562/ADR cells. This study provides a promising strategy to overcome drug resistance and deepens the understanding of the ceRNA regulatory mechanism related to drug resistance in CML cells.

[HIV prevalence and its associated factors among men who have sex with men in Chongqing].

OBJECTIVE: To examine HIV prevalence and its associated factors among men who have sex with men (MSM) and provide the evidence for the intervention program among MSM. METHODS: A face-to-face questionnaire interview was conducted among MSM recruited by snowball sampling method in Yuzhong, Jiulongpo and Shapingba district of Chongqing from July to September, 2007. Totally, 1044 MSM were recruited. Associated factors with HIV prevalence were analyzed using forward stepwise logistic regression that HIV status was the dependent variable and demographics, AIDS awareness, sexual behaviors and the status of the intervention were independent variables. RESULTS: A total of 1044 MSM were surveyed. The rate of AIDS awareness was 89.5% among MSM. The rate of unprotected anal sex during the past 6 months was 63.8%. The prevalence of HIV and syphilis was 8.5% (89/1044) and 12.5% (131/1044) respectively. The multivariate analysis identified that the older MSM (OR = 1.69, 95% CI: 1.13 - 2.52), junior school education (OR = 1.89, 95% CI: 1.17 - 3.05), younger than 18 years old of the first sex (OR = 3.11, 95% CI: 1.20 - 8.02), more than 10 sexual partners (OR = 2.24, 95% CI: 1.24 - 4.02), the history of having sex with women (OR = 2.40, 95% CI: 1.64 - 3.51) and syphilis infection (OR = 4.52, 95% CI: 2.77 - 7.38) were independent risk factors associated with HIV infection. CONCLUSION: The rate of unprotected anal sex was high, so were the prevalence of HIV and syphilis among MSM. It should be urgent to conduct the intervention to stop AIDS rapid transmission among MSM.