A Family of Novel miRNA-Like Small RNAs Dysregulated in Renal Cell Carcinoma.
Chao Guo, Xiwei Wu, Hanlin Gao, Bing Mu, Jennifer M Jin, Jinhui Wang, Massimo D'Apuzzo, Lawrence M Weiss, Huiqing Wu. City of Hope, Duarte, CA
Background: Small non-coding RNA (smRNA) is involved in almost every biological process, including developmental timing, cell differentiation, cell proliferation, cell death, metabolic control, transposon silencing and antiviral defence. Some smRNAs are derived from tRNA, snoRNA and introns. MicroRNA (miRNA) is a group of smRNAs that regulate gene expression. It is processed from its precursors which act as substrates for Drosha and Dicer. Incorporating with Argonaute (Ago) proteins to form a miRNA-induced silencing complex (miRISC), miRNAs base-pair to target mRNAs and induce their translational repression or deadenylation and degradation. Recent study has shown several human snoRNAs with miRNA-like functions.
Design: (1) Deep sequencing of smRNA populations co-immunoprecipitated with Ago2 protein and Dicer from renal cell carcinoma (RCC) cell lines (n=4); (2) functional characterization of selected smRNAs through a siRNA strategy; (3) whole genome smRNA and miRNA expression profiling by deep sequencing of a RCC frozen tissue cohort (n=12).
Results: (1) A population of smRNAs is bound to Ago2 protein and is associated with Dicer; (2) these smRNAs are composed of fragmented tRNA, rRNA, snoRNA, snRNA, scRNA, Mt-tRNA, introns and exons; (3) knock-down of several selected candidates from this smRNA family inhibits the proliferation of RCC cell lines; (4) in addition to known miRNAs, a number of these smRNAs are differentially expressed in RCC, as compared to benign renal tissue.
Conclusions: We have defined a novel family of smRNAs which are miRNA-like and are derived from other non-coding RNAs, introns and exons. This family of miRNA-like smRNAs is involved in regulation of RCC cell proliferation and is found to be aberrantly expressed in renal cell carcinoma, suggesting a functional role in RCC tumorigenesis.
Category: Special Category - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 1, 2011 8:30 AM
Platform Session: Section H 1, Tuesday Morning