Expression profiling of microRNAs (miRNAs) in most diseases might be popular and provide the possibility for diagnostic implication, but few studies have accurately quantified the expression level of dysregulated miRNAs in acute myeloid leukemia (AML). In this study, we analyzed the peripheral blood mononuclear cells (PBMCs) from 10 AML patients (subtypes M1 to M5) and six normal controls by miRNA microarray and identified several differentially expressed miRNAs. Among them miR-29a and miR-142-3p were selectively encountered in Northern blot analysis and their significantly decreased expression in AML was further confirmed. Quantitative real-time PCR in 52 primarily diagnosed AML patients and 100 normal controls not only verified the expression properties of these 2 miRNAs, but also established that the expression level of miR-142-3p and miR-29a in PBMCs could be used as novel diagnostic markers. A better diagnostic outcome was achieved by combining miR-29a and miR-142-3p with about 90% sensitivity, 100% specificity, and an area under the ROC curve (AUC) of 0.97. Our results provide insights into the involvement of miRNAs in leukemogenesis, and offer candidates for AML diagnosis and therapeutic strategy.

Genome-wide association studies indicate that many disease susceptibility regions reside in non-protein-coding regions of the genome. Long noncoding RNAs (lncRNAs) are a major component of the noncoding genome, but their biological impacts are not fully understood. Here, we performed a CRISPR interference (CRISPRi) screen on 2263 epidermis-expressed lncRNAs and identified nine novel candidate lncRNAs regulating keratinocyte proliferation. We further characterized a top hit from the screen, progenitor renewal associated non-coding RNA (PRANCR), using RNA interference-mediated knockdown and phenotypic analysis in organotypic human tissue. PRANCR regulates keratinocyte proliferation, cell cycle progression, and clonogenicity. PRANCR-deficient epidermis displayed impaired stratification with reduced expression of differentiation genes that are altered in human skin diseases, including keratins 1 and 10, filaggrin, and loricrin. Transcriptome analysis showed that PRANCR controls the expression of 1136 genes, with strong enrichment for late cell cycle genes containing a CHR promoter element. In addition, PRANCR depletion led to increased levels of both total and nuclear CDKN1A (also known as p21), which is known to govern both keratinocyte proliferation and differentiation. Collectively, these data show that PRANCR is a novel lncRNA regulating epidermal homeostasis and identify other lncRNA candidates that may have roles in this process as well.

A novel tyrosine aminotransferase gene (designated as SmTAT) involved in rosmarinic acid biosynthesis pathway is cloned from Salvia miltiorrhiza Bung. The full-length cDNA of SmTAT is 1,603 bp long with an open reading frame (ORF) of 1,233 bp encoding a polypeptide of 411 amino acid residues. The deduced amino acid sequence of the SmTAT gene shared high homology with other known TATs. Analysis of SmTAT genomic DNA reveals that it contains 6 exons, 5 introns. The analysis of SmTAT promoter region and terminator region was also presented. Semi-quantitative RT-PCR analysis reveals that the constitutive expression of SmTAT in stem is much higher than that in root, leaf. Further expression analysis reveals that the signaling components of defense/stress pathways, such as methyl jasmonate (MeJA), abscisic acid (ABA), salicylic acid (SA) and ultraviolet-B radiation (UV-B), up-regulate the SmTAT transcript levels over the control. This study provides useful information for further studying this gene and its function in rosmarinic acid biosynthetic pathway in S. miltiorrhiza, the roots of which so-called ''Danshen'' possess many pharmaceutical properties for human health.

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