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Distinct Profiles for Mitochondrial t-RNAs and Small Nucleolar RNAs in Locally Invasive and Metastatic Colorectal Cancer.

ABSTRACT: PURPOSE:To gain insight into factors involved in tumor progression and metastasis, we examined the role of noncoding RNAs in the biologic characteristics of colorectal carcinoma, in paired samples of tumor together with normal mucosa from the same colorectal carcinoma patient. The tumor and healthy tissue samples were collected and stored under stringent conditions, thereby minimizing warm ischemic time. EXPERIMENTAL DESIGN:We focused particularly on distinctions among high-stage tumors and tumors with known metastases, performing RNA-Seq analysis that quantifies transcript abundance and identifies novel transcripts. RESULTS:In comparing 35 colorectal carcinomas, including 9 metastatic tumors (metastases to lymph nodes and lymphatic vessels), with their matched healthy control mucosa, we found a distinct signature of mitochondrial transfer RNAs (MT-tRNA) and small nucleolar RNAs (snoRNA) for metastatic and high-stage colorectal carcinoma. We also found the following: (i) MT-TF (phenylalanine) and snord12B expression correlated with a substantial number of miRNAs and mRNAs in 14 colorectal carcinomas examined; (ii) an miRNA signature of oxidative stress, hypoxia, and a shift to glycolytic metabolism in 14 colorectal carcinomas, regardless of grade and stage; and (iii) heterogeneous MT-tRNA/snoRNA fingerprints for 35 pairs. CONCLUSIONS:These findings could potentially assist in more accurate and predictive staging of colorectal carcinoma, including identification of those colorectal carcinomas likely to metastasize.

SUBMITTER: Xu L

PROVIDER: S-EPMC4738054 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Distinct Profiles for Mitochondrial t-RNAs and Small Nucleolar RNAs in Locally Invasive and Metastatic Colorectal Cancer.

Xu Lai L Ziegelbauer Joseph J Wang Rong R Wu Wells W WW Shen Rong-Fong RF Juhl Hartmut H Zhang Yaqin Y Rosenberg Amy A

Clinical cancer research : an official journal of the American Association for Cancer Research 20150918 3

<h4>Purpose</h4>To gain insight into factors involved in tumor progression and metastasis, we examined the role of noncoding RNAs in the biologic characteristics of colorectal carcinoma, in paired samples of tumor together with normal mucosa from the same colorectal carcinoma patient. The tumor and healthy tissue samples were collected and stored under stringent conditions, thereby minimizing warm ischemic time.<h4>Experimental design</h4>We focused particularly on distinctions among high-stage ...[more]

PMID: 26384739

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Project description:Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs) are non-coding RNAs involved in the maturation of other RNA molecules and generally located in the introns of host genes. It is now emerging that altered sno/scaRNAs expression may play a pathological role in cancer. This study elucidates the patterns of sno/scaRNAs expression in multiple myeloma (MM), by profiling puri?ed malignant plasma cells from 55 MMs, 8 secondary plasma cell leukemias (sPCL) and 4 normal controls. Overall, a global sno/scaRNAs down-regulation was found in MMs and at more extent in sPCLs compared to normal plasma cells. Whereas SCARNA22 resulted the only sno/scaRNA characterizing the TC4 MM, TC2 group displayed a distinct sno/scaRNA signature overexpressing members of SNORD115 and SNORD116 families located in a region finely regulated by imprinting mechanism at 15q11. However, the imprinting center resulted overall hypomethylated in MMs independently of the SNORD115 and SNORD116 expression levels. Finally, integrative analyses with available gene expression and genome-wide data revealed the occurrence of significant sno/scaRNAs/host genes co-expression and the putative influence of allelic imbalances on specific snoRNAs expression. Our data extend the current view of sno/scaRNAs deregulation in cancer and add novel information into the bio-molecular complexity of plasma cell dyscrasias. This series of microarray experiments contains the gene expression profiles of purified plasma cells (PCs) obtained from 55 multiple myeloma (MM) and 8 secondary plasma cell leukemia (sPCL) at diagnosis. PCs were purified from bone marrow samples using CD138 immunomagnetic microbeads according to the manufacturer's instructions (MidiMACS system, Miltenyi Biotec); the purity of the positively selected PCs was assessed by morphology and flow cytometry and was > 90% in all cases. 5.5 micrograms of single-stranded DNA target obtained from 100 ng of purified total RNA was fragmented and then labeled using the WT Terminal Labeling Kit according to the standard Affymetrix protocol (GeneChipÂ® Whole Transcript (WT) Sense Target Labeling Assay Manual). The fragmented labeled single-stranded DNA target was hybridized for 16 hours and 30 minutes at 45Â°C on GeneChipÂ® Gene 1.0 ST array according to the standard Affymetrix protocol. Washing and scanning were performed using GeneChip System of Affymetrix (GeneChip Hybridization Oven 640, GeneChip Fluidics Station 450 and GeneChip Scanner 7G). The raw intensity expression values were processed by Robust Multi-array Average (RMA) complete procedure with the re-mapped Chip Definition Files (CDF) from BrainArray libraries version 15.0.0 available at http://brainarray.mbni.med.umich.edu/Brainarray/Database/CustomCDF/15.0.0/entrezg.asp.

Dataset Information

Distinct Profiles for Mitochondrial t-RNAs and Small Nucleolar RNAs in Locally Invasive and Metastatic Colorectal Cancer.

Publications

Distinct Profiles for Mitochondrial t-RNAs and Small Nucleolar RNAs in Locally Invasive and Metastatic Colorectal Cancer.

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