Small RNA sequencing revealed aberrant piRNA expression profiles in colorectal cancer

Obesity, the accumulation of body fat to excess, may cause serious negative health effects, including increased risk of heart disease, type 2 diabetes, stroke and certain cancers. The biology of obesity is complex and not well understood, involving both environmental and genetic factors and affecting metabolic and endocrine mechanisms in tissues of the gut, adipose, and brain. Previous RNA sequencing studies have identified transcripts associated with obesity and body mass index in blood and fat, often using animal models, but RNA sequencing studies in human brain tissue related to obesity have not been previously undertaken. We conducted both large and small RNA sequencing of hypothalamus (207 samples) and nucleus accumbens (276 samples) from individuals defined as consistently obese (124 samples), consistently normal weight as controls (148 samples) or selected without respect to BMI and falling within neither case nor control definition (211 samples), based on longitudinal BMI measures. The samples were provided by three cohort studies with brain donation programs; the Framingham Heart Study (FHS), the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). For each brain region and large/small RNA sequencing set, differential expression of obesity, BMI, brain region and sex was performed. Analyses were done transcriptome-wide as well as with a priori defined sets of obesity or BMI-associated mRNAs and microRNAs (miRNAs). There are sixteen mRNAs and five microRNAs that are differentially expressed (adjusted p < 0.05) by obesity or BMI in these tissues, several of which were validated with qPCR data. The results include many that are BMI-associated, such as APOBR and CES1, as well as many associated with the immune system and some with addiction, such as the gene sets 'cytokine signaling in immune system' and 'opioid signaling'. In spite of the relatively large number of samples, our study was likely under-powered to detect other transcripts or miRNA with relevant but smaller effects.

Download Full-text

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

10.1158/1538-7445.sabcs18-4012 ◽

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

Download Full-text

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

mSystems ◽

10.1128/msystems.00451-19 ◽

2020 ◽

Vol 5 (1) ◽

Cited By ~ 3

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.

Download Full-text

Small RNA sequencing and differential expression of miRNAs in colorectal cancer

Journal of Transdisciplinary Biomedicine ◽

10.24294/jtb.v1i2.4 ◽

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.

Download Full-text

5′-tRF-GlyGCC: a tRNA-derived small RNA as a novel biomarker for colorectal cancer diagnosis

Genome Medicine ◽

10.1186/s13073-021-00833-x ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Yingmin Wu ◽

Xiangling Yang ◽

Guanmin Jiang ◽

Haisheng Zhang ◽

Lichen Ge ◽

...

Keyword(s):

Colorectal Cancer ◽

Small Rna ◽

Expression Profiles ◽

Diagnostic Value ◽

Carbohydrate Antigen ◽

Small Rna Sequencing ◽

In Vivo Models ◽

Diagnostic Values

Abstract Background tRNA-derived small RNAs (tDRs), which are widely distributed in human tissues including blood and urine, play an important role in the progression of cancer. However, the expression of tDRs in colorectal cancer (CRC) plasma and their potential diagnostic values have not been systematically explored. Methods The expression profiles of tDRs in plasma of CRC and health controls (HCs) are investigated by small RNA sequencing. The level and diagnostic value of 5′-tRF-GlyGCC are evaluated by quantitative PCR in plasma samples from 105 CRC patients and 90 HCs. The mechanisms responsible for biogenesis of 5′-tRF-GlyGCC are checked by in vitro and in vivo models. Results 5′-tRF-GlyGCC is dramatically increased in plasma of CRC patients compared to that of HCs. The area under curve (AUC) for 5′-tRF-GlyGCC in CRC group is 0.882. The combination of carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) with 5′-tRF-GlyGCC improves the AUC to 0.926. Consistently, the expression levels of 5′-tRF-GlyGCC in CRC cells and xenograft tissues are significantly greater than that in their corresponding controls. Blood cells co-cultured with CRC cells or mice xenografted with CRC tumors show increased levels of 5′-tRF-GlyGCC. In addition, we find that the increased expression of 5′-tRF-GlyGCC is dependent on the upregulation of AlkB homolog 3 (ALKBH3), a tRNA demethylase which can promote tRNA cleaving to generate tDRs. Conclusions The level of 5′-tRF-GlyGCC in plasma is a promising diagnostic biomarker for CRC diagnosis.

Download Full-text

Differential miRNA Expression Profiles in Cumulus and Mural Granulosa Cells from Human Pre-ovulatory Follicles

MicroRNA ◽

10.2174/2211536607666180912152618 ◽

2018 ◽

Vol 8 (1) ◽

pp. 61-67 ◽

Cited By ~ 4

Author(s):

Daniela Andrei ◽

Roland A. Nagy ◽

Aafke van Montfoort ◽

Uwe Tietge ◽

Martijn Terpstra ◽

...

Keyword(s):

Rna Sequencing ◽

Granulosa Cells ◽

Small Rna ◽

Mirna Expression ◽

Target Gene ◽

Expression Profiles ◽

Cell Types ◽

Small Rna Sequencing ◽

Gene Sets ◽

Mirna Expression Profiles

Background: Mural Granulosa Cells (MGCs) and Cumulus Cells (CCs) are two specialized cell types that differentiate from a common progenitor during folliculogenesis. Although these two cell types have specialized functions and gene expression profiles, little is known about their microRNA (miRNA) expression patterns. Objective: To describe the miRNA profile of mural and cumulus granulosa cells from human preovulatory follicles. </P><P> Methods: Using small RNA sequencing, we defined the miRNA expression profiles of human primary MGCs and CCs, isolated from healthy women undergoing ovum pick-up for in vitro Fertilization (IVF). Results: Small RNA sequencing revealed the expression of several hundreds of miRNAs in MGCs and CCs with 53 miRNAs being significantly differentially expressed between MGCs and CCs. We validated the differential expression of miR-146a-5p, miR-149-5p, miR-509-3p and miR-182-5p by RT-qPCR. Analysis of proven targets revealed 37 targets for miR-146a-5p, 43 for miR-182-5p, 2 for miR-509-3p and 9 for miR-149-5p. Gene Ontology (GO) analysis for these 4 target gene sets revealed enrichment of 12 GO terms for miR-146a-5p and 10 for miR-182-5p. The GO term ubiquitin-like protein conjugation was enriched within both miRNA target gene sets. We generated miRNA expression profiles for MGCs and CCs and identified several differentially expressed miRNAs.

Download Full-text