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Deep Sequencing of Serum Small RNAs Identifies Patterns of 5' tRNA Half and YRNA Fragment Expression Associated with Breast Cancer.

Dhahbi JM, Spindler SR, Atamna H, Boffelli D, Martin DI - Biomark Cancer (2014)

Bottom Line: Small noncoding RNAs circulating in the blood may serve as signaling molecules because of their ability to carry out a variety of cellular functions.We used deep sequencing and informatics analysis to catalog small RNAs in the sera of breast cancer cases and normal controls. 5' tRNA halves and YRNA fragments are abundant in both groups, but we found that a breast cancer diagnosis is associated with changes in levels of specific subtypes.We find significant changes in the levels of specific 5' tRNA halves and YRNA fragments associated with clinicopathologic characteristics of the cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of California at Riverside, Riverside, CA, USA. ; Center for Genetics, Children's Hospital Oakland Research Institute, Oakland, CA, USA.

ABSTRACT
Small noncoding RNAs circulating in the blood may serve as signaling molecules because of their ability to carry out a variety of cellular functions. We have previously described tRNA- and YRNA-derived small RNAs circulating as components of larger complexes in the blood of humans and mice; the characteristics of these small RNAs imply specific processing, secretion, and physiological regulation. In this study, we have asked if changes in the serum abundance of these tRNA and YRNA fragments are associated with a diagnosis of cancer. We used deep sequencing and informatics analysis to catalog small RNAs in the sera of breast cancer cases and normal controls. 5' tRNA halves and YRNA fragments are abundant in both groups, but we found that a breast cancer diagnosis is associated with changes in levels of specific subtypes. This prompted us to look at existing sequence datasets of serum small RNAs from 42 breast cancer cases, taken at the time of diagnosis. We find significant changes in the levels of specific 5' tRNA halves and YRNA fragments associated with clinicopathologic characteristics of the cancer. Although these findings do not establish causality, they suggest that circulating 5' tRNA halves and YRNA fragments with known cellular functions may participate in breast cancer syndromes and have potential as circulating biomarkers. Larger studies with multiple types of cancer are needed to adequately evaluate their potential use for the development of noninvasive cancer screening.

No MeSH data available.


Related in: MedlinePlus

Length distribution and annotation of reads from serum small RNAs of five healthy females and five females diagnosed with breast cancer. Length of mapped reads from five normal (A) and five cancer samples (B) is plotted against read abundance. Colors of the bars denote the individual sources of the serum small RNAs (normal and breast cancer samples). (C) Length distribution of pooled sequencing reads from all 10 samples plotted against abundance of reads according to their annotation. Length distribution is plotted against abundance of the reads annotated as miRNAs, YRNAs, tRNAs, rRNAs, or other sRNAs (snRNAs and snoRNAs). (D) Pie chart showing the percent of reads (pooled from both normal and breast cancer) mapping to the indicated specific types of small RNAs. (E) Pie chart showing the percent of reads mapping to the indicated types of small RNAs in pooled datasets obtained by sequencing of small RNAs in the sera of 42 newly diagnosed breast cancer cases.
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f1-bic-6-2014-037: Length distribution and annotation of reads from serum small RNAs of five healthy females and five females diagnosed with breast cancer. Length of mapped reads from five normal (A) and five cancer samples (B) is plotted against read abundance. Colors of the bars denote the individual sources of the serum small RNAs (normal and breast cancer samples). (C) Length distribution of pooled sequencing reads from all 10 samples plotted against abundance of reads according to their annotation. Length distribution is plotted against abundance of the reads annotated as miRNAs, YRNAs, tRNAs, rRNAs, or other sRNAs (snRNAs and snoRNAs). (D) Pie chart showing the percent of reads (pooled from both normal and breast cancer) mapping to the indicated specific types of small RNAs. (E) Pie chart showing the percent of reads mapping to the indicated types of small RNAs in pooled datasets obtained by sequencing of small RNAs in the sera of 42 newly diagnosed breast cancer cases.

Mentions: We used breast cancer to explore the possibility that changes in circulating 5′ tRNA halves and 5′ YRNA fragments, besides circulating miRNAs, can be associated with a disease state. We deep sequenced serum small RNAs and compared levels of the various types of circulating small RNAs in five breast cancer and five control subjects. The breast cancer subjects were a diverse group, and some samples were obtained after treatment (Table 1). Sequencing reads from each serum sample were aligned to the human genome. The size distribution of aligned reads revealed three peaks, at 20–24 nt, 25–29 nt, and 30–33 nt, in both normal and cancer groups (Fig. 1A and B). The peak pattern is similar to the pattern we recently reported in the human and mouse sera.10,11


Deep Sequencing of Serum Small RNAs Identifies Patterns of 5' tRNA Half and YRNA Fragment Expression Associated with Breast Cancer.

Dhahbi JM, Spindler SR, Atamna H, Boffelli D, Martin DI - Biomark Cancer (2014)

Length distribution and annotation of reads from serum small RNAs of five healthy females and five females diagnosed with breast cancer. Length of mapped reads from five normal (A) and five cancer samples (B) is plotted against read abundance. Colors of the bars denote the individual sources of the serum small RNAs (normal and breast cancer samples). (C) Length distribution of pooled sequencing reads from all 10 samples plotted against abundance of reads according to their annotation. Length distribution is plotted against abundance of the reads annotated as miRNAs, YRNAs, tRNAs, rRNAs, or other sRNAs (snRNAs and snoRNAs). (D) Pie chart showing the percent of reads (pooled from both normal and breast cancer) mapping to the indicated specific types of small RNAs. (E) Pie chart showing the percent of reads mapping to the indicated types of small RNAs in pooled datasets obtained by sequencing of small RNAs in the sera of 42 newly diagnosed breast cancer cases.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4260766&req=5

f1-bic-6-2014-037: Length distribution and annotation of reads from serum small RNAs of five healthy females and five females diagnosed with breast cancer. Length of mapped reads from five normal (A) and five cancer samples (B) is plotted against read abundance. Colors of the bars denote the individual sources of the serum small RNAs (normal and breast cancer samples). (C) Length distribution of pooled sequencing reads from all 10 samples plotted against abundance of reads according to their annotation. Length distribution is plotted against abundance of the reads annotated as miRNAs, YRNAs, tRNAs, rRNAs, or other sRNAs (snRNAs and snoRNAs). (D) Pie chart showing the percent of reads (pooled from both normal and breast cancer) mapping to the indicated specific types of small RNAs. (E) Pie chart showing the percent of reads mapping to the indicated types of small RNAs in pooled datasets obtained by sequencing of small RNAs in the sera of 42 newly diagnosed breast cancer cases.
Mentions: We used breast cancer to explore the possibility that changes in circulating 5′ tRNA halves and 5′ YRNA fragments, besides circulating miRNAs, can be associated with a disease state. We deep sequenced serum small RNAs and compared levels of the various types of circulating small RNAs in five breast cancer and five control subjects. The breast cancer subjects were a diverse group, and some samples were obtained after treatment (Table 1). Sequencing reads from each serum sample were aligned to the human genome. The size distribution of aligned reads revealed three peaks, at 20–24 nt, 25–29 nt, and 30–33 nt, in both normal and cancer groups (Fig. 1A and B). The peak pattern is similar to the pattern we recently reported in the human and mouse sera.10,11

Bottom Line: Small noncoding RNAs circulating in the blood may serve as signaling molecules because of their ability to carry out a variety of cellular functions.We used deep sequencing and informatics analysis to catalog small RNAs in the sera of breast cancer cases and normal controls. 5' tRNA halves and YRNA fragments are abundant in both groups, but we found that a breast cancer diagnosis is associated with changes in levels of specific subtypes.We find significant changes in the levels of specific 5' tRNA halves and YRNA fragments associated with clinicopathologic characteristics of the cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of California at Riverside, Riverside, CA, USA. ; Center for Genetics, Children's Hospital Oakland Research Institute, Oakland, CA, USA.

ABSTRACT
Small noncoding RNAs circulating in the blood may serve as signaling molecules because of their ability to carry out a variety of cellular functions. We have previously described tRNA- and YRNA-derived small RNAs circulating as components of larger complexes in the blood of humans and mice; the characteristics of these small RNAs imply specific processing, secretion, and physiological regulation. In this study, we have asked if changes in the serum abundance of these tRNA and YRNA fragments are associated with a diagnosis of cancer. We used deep sequencing and informatics analysis to catalog small RNAs in the sera of breast cancer cases and normal controls. 5' tRNA halves and YRNA fragments are abundant in both groups, but we found that a breast cancer diagnosis is associated with changes in levels of specific subtypes. This prompted us to look at existing sequence datasets of serum small RNAs from 42 breast cancer cases, taken at the time of diagnosis. We find significant changes in the levels of specific 5' tRNA halves and YRNA fragments associated with clinicopathologic characteristics of the cancer. Although these findings do not establish causality, they suggest that circulating 5' tRNA halves and YRNA fragments with known cellular functions may participate in breast cancer syndromes and have potential as circulating biomarkers. Larger studies with multiple types of cancer are needed to adequately evaluate their potential use for the development of noninvasive cancer screening.

No MeSH data available.


Related in: MedlinePlus