Identification of HIV1-specific cascaded microRNA-mRNA regulatory relationships by parallel mRNA and microRNA expression profiling with AIDS patients after antiviral treatment. Homo sapiens

The molecular pathogenesis of infection by HIV (human immunodeficiency virus) is extremely complex and is not clearly defined despite intensive research efforts. MiRNA as a class of regulators in cancer development can affect multiple gene pathways by targeting various mRNAs. Thus, studies aimed at transcription and regulation after antiviral treatment combined with beneficial researches related to miRNAs are required. With the purpose of identifying the cascaded miRNA-mRNA regulatory relationships related to infection of HIV in gene level, the parallel miRNA and mRNA expression profiles were analyzed in our study. The differential expressed miRNAs and mRNAs were selected primarily. The differentially regulated miRNA-mRNA interactions were further identified according to the Pearson correlation analysis of gene expression level. In our study, the calculation of the regulatory impact factors (RIF) was also conducted, and it revealed several essential regulators related to antiviral treatment with AIDS. To give a further insight into these TF (transcription factors) regulators, the co-expression gene modules were identified using a threshold-based hierarchical clustering method. Meanwhile, the regulatory network was generated during the computing process. Understanding these regulatory elements may bear significant implications on understanding the pathogenesis of AIDS occurrence. Overall design: The microarray profiles utilized in our study is derived from Chengdu University of TCM in Sichuan, China. All donors as experimental group are confirmed as AIDS clinical patients according to 1994 revised classification system for HIV infection in America using protein western blotting by local epidemic station. The diagnosis standards to patients were referred to the Guidelines for Diagnosis and Treatment of HIV/AIDS in China (2005). The patients were accepted if they conformed to the following criteria: (a) corresponding to the criteria for diagnosis and treatment of HIV/AIDS; (b) ranging in age from 4 to 78 years old; (c) agreeing to sign an informed consent form. In our study, there are fifty AIDS patients and seven healthy persons as control group donated blood samples. Controls were all healthy, HIV-1-negative donors. Whereas, two more representative groups named LVL and HVL were further defined according to the viral load of the patients in order to explore the relationship between virus load and gene expression level after antiviral therapy. The LVL group includes 14 samples from patients while HVL group includes 16 AIDS samples. In addition, a further 36 independent blood samples from 33 AIDS patients and 3 healthy donors were applied to test and verify the accuracy of the differential expression results. The clinical characteristics of the three groups (CON, LVL and HVL) were assumed in Table 6. The majority of HIV-positive carriers being treated with ART (antiretroviral therapy) as in-patients got improvements of the AIDS disease in our research. mRNA and miRNA profiling of three groups: CON (n=7), LVL (n=14), HVL (n=16).