Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA‐induced silencing complex (RISC) components argonaute‐1, argonaute‐2, PACT, TARBP1, and TARBP2 in epithelial skin cancer

The microprocessor complex mediates intranuclear biogenesis of precursor microRNAs from the primary microRNA transcript. Extranuclear, mature microRNAs are incorporated into the RNA‐induced silencing complex (RISC) before interaction with complementary target mRNA leads to transcriptional repression or cleavage. In this study, we investigated the expression profiles of the microprocessor complex subunit DiGeorge syndrome critical region gene 8 (DGCR8) and the RISC components argonaute‐1 (AGO1), argonaute‐2 (AGO2), as well as double‐stranded RNA‐binding proteins PACT, TARBP1, and TARBP2 in epithelial skin cancer and its premalignant stage. Patients with premalignant actinic keratoses (AK, n = 6), basal cell carcinomas (BCC, n = 15), and squamous cell carcinomas (SCC, n = 7) were included in the study. Punch biopsies were harvested from the center of the tumors (lesional), from healthy skin sites (intraindividual controls), and from healthy skin sites in a healthy control group (n = 16; interindividual control). The DGCR8, AGO1, AGO2, PACT, TARBP1, and TARBP2 mRNA expression levels were detected by quantitative real‐time reverse transcriptase polymerase chain reaction. The DGCR8, AGO1, AGO2, PACT, and TARBP1 expression levels were significantly higher in the AK, BCC, and SCC groups than the healthy controls (P < 0.05). There was no significant difference in the TARBP2 expression levels between groups (P > 0.05). This study indicates that major components of the miRNA pathway, such as the microprocessor complex and RISC, are dysregulated in epithelial skin cancer. © 2011 Wiley Periodicals, Inc.

[1]  T. Gambichler,et al.  Immunohistochemical expression patterns of the microRNA-processing enzyme Dicer in cutaneous malignant melanomas, benign melanocytic nevi and dysplastic melanocytic nevi. , 2011, European journal of dermatology : EJD.

[2]  J. Doudna,et al.  Substrate-specific kinetics of Dicer-catalyzed RNA processing. , 2010, Journal of molecular biology.

[3]  Steven S. Chang,et al.  EIF2C Is Overexpressed and Amplified in Head and Neck Squamous Cell Carcinoma , 2010, ORL.

[4]  T. Gambichler,et al.  Expression Levels of the microRNA Processing Enzymes Drosha and Dicer in Epithelial Skin Cancer , 2010, Cancer investigation.

[5]  Chaohui Yu,et al.  Argonaute proteins: potential biomarkers for human colon cancer , 2010, BMC Cancer.

[6]  G. Peters,et al.  The double-stranded RNA-binding protein, PACT, is required for postnatal anterior pituitary proliferation , 2009, Proceedings of the National Academy of Sciences.

[7]  D. Purcell,et al.  Bmc Molecular Biology Characterization of the Trbp Domain Required for Dicer Interaction and Function in Rna Interference , 2022 .

[8]  T. Gambichler,et al.  MicroRNAs and the skin: tiny players in the body's largest organ. , 2009, Journal of dermatological science.

[9]  Carla Oliveira,et al.  A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function , 2009, Nature Genetics.

[10]  D. Haussler,et al.  Posttranscriptional Crossregulation between Drosha and DGCR8 , 2009, Cell.

[11]  T. Dalmay,et al.  MicroRNAs and cancer , 2008, Journal of internal medicine.

[12]  L. Joshua-Tor,et al.  Argonautes confront new small RNAs. , 2007, Current opinion in chemical biology.

[13]  Leonard D. Goldstein,et al.  Global microRNA profiles in cervical squamous cell carcinoma depend on Drosha expression levels , 2007, The Journal of pathology.

[14]  A. Bode,et al.  Involvement of ERKs, RSK2 and PKR in UVA-induced signal transduction toward phosphorylation of eIF2alpha (Ser(51)). , 2007, Carcinogenesis.

[15]  Rudolf Jaenisch,et al.  DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal , 2007, Nature Genetics.

[16]  A. Gartel,et al.  RNA interference in cancer. , 2006, Biomolecular engineering.

[17]  V. Kim,et al.  The role of PACT in the RNA silencing pathway , 2006, The EMBO journal.

[18]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[19]  V. Kim,et al.  The Drosha-DGCR8 complex in primary microRNA processing. , 2004, Genes & development.

[20]  R. Shiekhattar,et al.  The Microprocessor complex mediates the genesis of microRNAs , 2004, Nature.

[21]  D. Bartel MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[22]  B. Cullen,et al.  Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. , 2003, Genes & development.

[23]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[24]  Mingli Yang,et al.  RAX, a Cellular Activator for Double-stranded RNA-dependent Protein Kinase during Stress Signaling* , 1999, The Journal of Biological Chemistry.