Abstract 4012: Small RNA-sequencing identifies a microRNA signature predictive of response to FOLFOX-based adjuvant therapy in stage II and III colorectal cancer

2019 ◽  
Author(s):  
Raju Kandimalla ◽  
Uthra Balaji ◽  
Jinghua Gu ◽  
Marta Mendiola ◽  
Francesc Balaguer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Therapy ◽  
Rna Sequencing ◽  
Small Rna ◽  
Stage Ii ◽  
Small Rna Sequencing

scholarly journals Human Colon Mucosal Biofilms and Murine Host Communicate via Altered mRNA and microRNA Expression during Cancer

mSystems ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Sarah Tomkovich ◽  
Raad Z. Gharaibeh ◽  
Christine M. Dejea ◽  
Jillian L. Pope ◽  
Jinmai Jiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Microbial Communities ◽  
Rna Sequencing ◽  
Small Rna ◽  
Intestinal Bacteria ◽  
Distal Colon ◽  
Human Colon ◽  
Small Rna Sequencing ◽  
Microrna Sequencing

ABSTRACT Disrupted interactions between host and intestinal bacteria are implicated in colorectal cancer (CRC) development. However, activities derived from these bacteria and their interplay with the host are unclear. Here, we examine this interplay by performing mouse and microbiota RNA sequencing on colon tissues and 16S and small RNA sequencing on stools from germfree (GF) and gnotobiotic ApcMinΔ850/+;Il10−/− mice associated with microbes from biofilm-positive human CRC tumor (BF+T) and biofilm-negative healthy (BF-bx) tissues. The bacteria in BF+T mice differentially expressed (DE) >2,900 genes, including genes related to bacterial secretion, virulence, and biofilms but affected only 62 host genes. Small RNA sequencing of stools from these cohorts revealed eight significant DE host microRNAs (miRNAs) based on biofilm status and several miRNAs that correlated with bacterial taxon abundances. Additionally, computational predictions suggest that some miRNAs preferentially target bacterial genes while others primarily target mouse genes. 16S rRNA sequencing of mice that were reassociated with mucosa-associated communities from the initial association revealed a set of 13 bacterial genera associated with cancer that were maintained regardless of whether the reassociation inoculums were initially obtained from murine proximal or distal colon tissues. Our findings suggest that complex interactions within bacterial communities affect host-derived miRNA, bacterial composition, and CRC development. IMPORTANCE Bacteria and bacterial biofilms have been implicated in colorectal cancer (CRC), but it is still unclear what genes these microbial communities express and how they influence the host. MicroRNAs regulate host gene expression and have been explored as potential biomarkers for CRC. An emerging area of research is the ability of microRNAs to impact growth and gene expression of members of the intestinal microbiota. This study examined the bacteria and bacterial transcriptome associated with microbes derived from biofilm-positive human cancers that promoted tumorigenesis in a murine model of CRC. The murine response to different microbial communities (derived from CRC patients or healthy people) was evaluated through RNA and microRNA sequencing. We identified a complex interplay between biofilm-associated bacteria and the host during CRC in mice. These findings may lead to the development of new biomarkers and therapeutics for identifying and treating biofilm-associated CRCs.

scholarly journals Small RNA sequencing and differential expression of miRNAs in colorectal cancer

2017 ◽  
Vol 1 (2) ◽  
Author(s):  
Kwan-Liang Lye ◽  
Shiran Mohd Sidik ◽  
Sabariah Abdul Rahman ◽  
Yoke-Kqueen Cheah
Keyword(s):  
Colorectal Cancer ◽  
Rna Sequencing ◽  
Small Rna ◽  
Mirna Expression Profile ◽  
Small Rna Sequencing ◽  
Illumina Hiseq ◽  
Sequencing Platform ◽  
Normal Tissues ◽  
Cellular Processes ◽  
Generation Sequencing

MicroRNAs (miRNAs) are small, non-coding RNAs that are involved in various cellular processes. Many studies have shown that miRNAs are dysregulated in various types of cancer. In Malaysia, there are no published studies on miRNA expression profile for colorectal cancer, which is among the most common cancer here and other parts of the world. Next-generation sequencing platform was introduced in recent years and has revolutionized the biomedical research settings. In this study, we performed small RNA sequencing on Illumina HiSeq 2000 platform and found that 22 miRNAs were significantly differential expressed between cancer and normal tissues. Further validation on qRT-PCR on 5 of the miRNAs selected showed 3 of them were up-regulated (hsa-miR-106a, hsa-miR-135b, hsa-miR-21) while 2 were down-regulated (hsa-miR1, hsa-miR-504). These findings may lead to a simple profiling method to distinguish the risk of imdividuals in developing colorectal cancer.

scholarly journals Small RNA sequencing revealed aberrant piRNA expression profiles in colorectal cancer

2019 ◽  
Author(s):  
Jie Yin ◽  
Wei Qi ◽  
Chen‑Guang Ji ◽  
Dong‑Xuan Zhang ◽  
Xiao‑Li Xie ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rna Sequencing ◽  
Small Rna ◽  
Expression Profiles ◽  
Small Rna Sequencing

Small RNA Sequencing to Discover Circulating MicroRNA Biomarkers of Testicular Toxicity in Dogs

2020 ◽  
pp. 109158182096151
Author(s):  
Jennifer C. Shing ◽  
Kai Schaefer ◽  
Shaun E. Grosskurth ◽  
Andy H. Vo ◽  
Tatiana Sharapova ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Small Rna ◽  
Exploratory Study ◽  
Quantitative Polymerase Chain Reaction ◽  
Small Rna Sequencing ◽  
Circulating Microrna ◽  
Testicular Toxicity ◽  
Potential Candidate ◽  
Drug Induced ◽  
Organ Systems

Predictive indicators of testicular toxicity could improve drug development by allowing early in-life screening for this adverse effect before it becomes severe. We hypothesized that circulating microRNAs (miRNAs) could serve as testicular toxicity biomarkers in dogs. Herein, we describe the results of an exploratory study conducted to discover biomarkers of drug-induced testicular injury. Following a dose-selection study using the testicular toxicant ethylene glycol monomethyl ether (EGME), we chose a dose of 50 mg/kg/d EGME to avoid systemic toxicity and treated 2 groups of dogs (castrated, non-castrated) for 14 to 28 days. Castrated animals were used as negative controls to identify biomarkers specific for testicular toxicity because EGME can cause toxicity to organ systems in addition to the testis. Blood was collected daily during the dosing period, followed by recovery for 29 to 43 days with less frequent sampling. Dosing was well tolerated, resulting in mild-to-moderate degeneration in testes and epididymides. Global profiling of serum miRNAs at selected dosing and recovery time points was completed by small RNA sequencing. Bioinformatics data analysis using linear modeling demonstrated several circulating miRNAs that were differentially abundant during the dosing period compared with baseline and/or castrated control samples. Confirmatory reverse transcription quantitative polymerase chain reaction data in these animals was unable to detect sustained alterations of miRNAs in serum, except for 1 potential candidate cfa-miR-146b. Taken together, we report the results of a comprehensive exploratory study and suggest future directions for follow-up research to address the challenge of developing diagnostic biomarkers of testicular toxicity.

scholarly journals Small RNA-Sequencing: Approaches and Considerations for miRNA Analysis

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 964
Author(s):  
Sarka Benesova ◽  
Mikael Kubista ◽  
Lukas Valihrach
Keyword(s):  
Rna Sequencing ◽  
Small Rna ◽  
High Sensitivity ◽  
Small Rna Sequencing ◽  
Rna Seq ◽  
Liquid Biopsies ◽  
Comprehensive Overview ◽  
Rna Molecules ◽  
Novel Mirna ◽  
The Many

MicroRNAs (miRNAs) are a class of small RNA molecules that have an important regulatory role in multiple physiological and pathological processes. Their disease-specific profiles and presence in biofluids are properties that enable miRNAs to be employed as non-invasive biomarkers. In the past decades, several methods have been developed for miRNA analysis, including small RNA sequencing (RNA-seq). Small RNA-seq enables genome-wide profiling and analysis of known, as well as novel, miRNA variants. Moreover, its high sensitivity allows for profiling of low input samples such as liquid biopsies, which have now found applications in diagnostics and prognostics. Still, due to technical bias and the limited ability to capture the true miRNA representation, its potential remains unfulfilled. The introduction of many new small RNA-seq approaches that tried to minimize this bias, has led to the existence of the many small RNA-seq protocols seen today. Here, we review all current approaches to cDNA library construction used during the small RNA-seq workflow, with particular focus on their implementation in commercially available protocols. We provide an overview of each protocol and discuss their applicability. We also review recent benchmarking studies comparing each protocol’s performance and summarize the major conclusions that can be gathered from their usage. The result documents variable performance of the protocols and highlights their different applications in miRNA research. Taken together, our review provides a comprehensive overview of all the current small RNA-seq approaches, summarizes their strengths and weaknesses, and provides guidelines for their applications in miRNA research.

scholarly journals Identification of Zinc Deficiency-Responsive MicroRNAs in Brassica juncea Roots by Small RNA Sequencing

2013 ◽  
Vol 12 (11) ◽  
pp. 2036-2044 ◽  
Author(s):  
Dong-qing SHI ◽  
Yuan ZHANG ◽  
Jin-hu MA ◽  
Yu-long LI ◽  
Jin XU
Keyword(s):  
Rna Sequencing ◽  
Brassica Juncea ◽  
Zinc Deficiency ◽  
Small Rna ◽  
Small Rna Sequencing

Abstract 46: High-Density Lipoproteins Control Monocyte Differentiation Through microRNA Intercellular Communication

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Kasey C Vickers ◽  
Michael G Levin ◽  
Michael P Anderson ◽  
Qing Xu ◽  
Joshua Anzinger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Sequencing ◽  
High Throughput ◽  
Small Rna ◽  
Cellular Response ◽  
Culture Media ◽  
Recipient Cell ◽  
Inflammatory Cells ◽  
High Density Lipoproteins ◽  
Small Rna Sequencing

Many HDL-microRNAs (miRNA) are well-characterized post-transcriptional regulators of inflammation, and are significantly increased on HDL with hypercholesterolemia and atherosclerosis in humans and mice. Therefore, we hypothesize that inflammatory cells uniquely control their own gene expression through cellular miRNA export to HDL and then regulate recipient cell gene expression through HDL-mediated miRNA delivery. To test this hypothesis, we used high-throughput proteomics, Open Arrays, small RNA sequencing, and gene expression microarrays. Human monocytes (plasma elutriation) were differentiated into dendritic cells and multiple macrophage phenotypes. Each cell-type was incubated with pure reconstituted HDL (rHDL), which was then purified from culture media by apolipoprotein A-I immunoprecipitation after 24 h, and both cellular and HDL-miRNAs were profiled using TaqMan Open Arrays. Macrophages were found to export high levels of miRNAs to HDL that inhibit monocyte/macrophage differentiation (miR-146a, miR-223); however, monocytes were also found to export many miRNAs associated with differentiation, including miR-92a, miR-222, miR-17, miR-20a, miR106a, and miR-21. Furthermore, many miRNAs were found to be transcribed in inflammatory cells, but completely exported to HDL and not retained in the cell. Most interestingly, HDL treatment was found to induce miR-223 transcription in monocytes, as determined by primary miR-223 transcript levels; however, intracellular levels of the mature form (miR-223) did not change. These results suggest that HDL induces the export of miRNAs it transports. PAR-CLIP with high-throughput small RNA sequencing was used to demonstrate that miRNAs are transferred from macrophages to endothelial cells and loaded onto cellular Argonaute 2-continaining RNA-induced silencing complexes. To demonstrate this in mice, human HDL, containing endogenous levels of miR-223, were injected into miR-223-null mice and inflammation-associated miRNA delivery was mapped in vivo. In summary, we found profound differences in the cellular response to HDL treatment and HDL-miRNA communication amongst inflammatory cell phenotypes that are physiologically relevant to cardiovascular disease.

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