Rr-1, a Novel Ribosomal RNA-Derived Small Non-Coding RNA, Is Involved in Renal Cell Carcinoma Metastasis
Yuping Li, Xiwei Wu, Hanlin Gao, Chao Guo, Jennifer M Jin, Frances Wang, Bing Mu, Xuejun Li, Jinhui Wang, Massimo D'Apuzzo, Lawrence M Weiss, Huiqing Wu. City of Hope National Medical Center and Beckman Research Institute, Duarte, CA; Third Military Medical University, Chongqing, China
Background: Small non-coding RNAs (smRNAs) are involved in almost every biological process. SmRNAs that are involved in RNA interference (RNAi) are characteristically associated with Argonaut family proteins and function as the core of RNA-induced silencing complex (RISC). Some smRNAs have been reported to be derived from tRNAs, snoRNAs and introns. By deep sequencing of Ago2-bound small RNA fragments in renal cell carcinoma (RCC) cell lines, we have found a group of smRNAs to be derived from tRNAs, rRNAs, snoRNAs, snRNAs, scRNAs, Mt-tRNAs, introns and exons. We have also found many of them to be Dicer-associated and to be differentially expressed in localized and metastatic RCCs. Here, we report the study to characterize Rr-1, an rRNA-derived smRNA (rd-smRNA), in RCC metastasis.
Design: (1) Explore the structure of Rr-1 and its potential immediate precursor in rRNA by bioinformatics and laboratory studies. (2) Examine and validate Rr-1 differential expression in benign kidney tissue, localized and metastatic RCCs in an RCC frozen tissue cohort (n=24) using our whole genome smRNA deep sequencing data. (3) Characterize the function of Rr-1 on cell proliferation, migration and invasion by knocking down Rr-1 expression in ACHN, a metastatic RCC-derived cell line. (4) Investigate Rr-1-associated pathways by whole genome mRNA deep sequencing of Rr-1 knockdown metastatic RCC cells.
Results: (1) Rr-1 is found to be derived from 18S rRNA which harbors the potential Rr-1 immediate precursor in one of its stem loop structure. (2) Rr-1 is differentially expressed in benign kidney tissue, localized and metastatic RCCs. (3) Knockdown of Rr-1 significantly inhibits the cell proliferation, migration and invasion in metastatic RCC cells. (4) Knockdown of Rr-1 affects expression of a group of genes involved in cell cycle-related pathways.
Conclusions: We are the fist to report that Rr-1, a novel rd-smRNA, is involved in RCC metastasis by affecting metastatic tumor cell proliferation, migration and invasion through cell cycle-related pathways. This finding broadens our view of the function of smRNA and rRNA in tumorigenesis and metastasis.
Category: Special Category - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 277, Tuesday Morning