Identification of the Key Molecular Drivers of Phosphorus Utilization Based on Host miRNA-mRNA and Gut Microbiome Interactions
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Authors: Ponsuksili, Siriluck; Reyer, Henry; Hadlich, Frieder; Weber, Frank; Trakooljul, Nares; Oster, Michael; Siengdee, Puntita; Murani, Eduard; Rodehutscord, Markus; Camarinha-Silva, Amelia; Bennewitz, Joern; Wimmers, Klaus
Abstract
Phosphorus is an essential mineral for all living organisms and a limited resource worldwide. Variation and heritability of phosphorus utilization (PU) traits were observed, indicating the general possibility of improvement. Molecular mechanisms of PU, including host and microbial effects, are still poorly understood. The most promising molecules that interact between the microbiome and host are microRNAs. Japanese quail representing extremes for PU were selected from an F2 population for miRNA profiling of the ileal tissue and subsequent association with mRNA and microbial data of the same animals. Sixty-nine differentially expressed miRNAs were found, including 21 novel and 48 known miRNAs. Combining miRNAs and mRNAs based on correlated expression and target prediction revealed enrichment of transcripts in functional pathways involved in phosphate or bone metabolism such as RAN, estrogen receptor and Wnt signaling, and immune pathways. Out of 55 genera of microbiota, seven were found to be differentially abundant between PU groups. The study reveals molecular interactions occurring in the gut of quail which represent extremes for PU including miRNA-16-5p, miR-142b-5p, miR-148a-3p, CTDSP1, SMAD3, IGSF10, Bacteroides, and Alistipes as key indicators due to their trait-dependent differential expression and occurrence as hub-members of the network of molecular drivers of PU.
Identification of commonly regulated genes and biological pathways as potential targets in PC-3 and DU145 androgen-independent human prostate cancer cells treated with the curcumin analogue 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE
Authors: Citalingam, Kamini; Abas, Faridah; Lajis, Nordin H.; Othman, Iekhsan; Naidu, Rakesh
Abstract
Diarylpentanoid [l,5-bis(2-hydroxyphenyl)-l,4-pentadiene-3-one] (MS17) demonstrated enhanced anticancer activity compared to curcumin but its effect on androgen-independent prostate cancer has not been well-studied. The present study was aimed to perform gene expression profiling on MS 17 treated PC-3 and DU 145 cells using microarray technology to identify mutually regulated genes as common targets in both androgen-independent prostate cancer cell lines as well as molecular pathways that contributes to the anticancer activity of MS17. The profiling data revealed a dose-dependent gene regulation, evident by higher fold change expression values when the treatment dose was increased by 15-fold in both cell lines. Gene ontology classification was performed on highly regulated differentially expressed genes (DEGs). Among these genes, the mutually regulated DEGs were identified as common targets in both cell lines. The mutually up-regulated DEGs included, CRYAB and DNAI2 associated with cytoskeletal organization, HSPA6 and HSPB8 with response to unfolded protein, MMP3 and MMP10 with proteolysis, CACNA1G with transporter activity, NGFR with apoptosis, CCL26 with immune response, DNAJA4 with protein folding and TRIML2 with protein ubiquitination. However, the down-regulated genes such as CTDSP1 were associated with phosphatase activity, HIST1H2BFand HIST1H2AI with chromosome organization, MXD3 with regulation of transcription and TNFRSF6B with apoptosis. PC-3 and DU145 are androgen-independent prostate cancer cells with different biological properties, and identification of common targets in both cell lines could potentially be used as therapeutic targets. Pathway analysis of the DEGs in PC-3 cells demonstrated modulation of top pathways associated with cell cycle checkpoint, DNA damage, and inflammatory response while in DU145 cells the pathways were associated with immune response and metabolism. Thus, the findings of the present study provide insight into the antitumor activity of MS17 and as a potential chemotherapeutic agent for androgen independent prostate cancer cells.