Different signatures of miR-16, miR-30b and miR-93 in exosomes from breast cancer and DCIS patients

Qingtao Ni,Ines Stevic,Chi Pan,Volkmar Müller,Leticia Oliveira-Ferrer,Klaus Pantel,Heidi Schwarzenbach

doi:10.1038/s41598-018-31108-y

Qingtao Ni, Ines Stevic + Show 5 more

Open Access

https://doi.org/10.1038/s41598-018-31108-y

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Abstract

Loading of microRNAs (miRNAs) into exosomes that are involved in cellular communication is a selective process. The current study investigates whether the enrichment of miRNAs in exosomes reflects the pathogenesis of breast cancer (BC) and ductal carcinoma in situ (DCIS). The levels of miRNAs were quantified in exosomes from plasma of 32 BC patients, 8 DCIS patients and 8 healthy women by TaqMan real-time PCR-based miRNA array cards containing 47 different miRNAs. Then, exosomal miR-16, miR-30b and miR-93 that displayed deregulation in the arrays were selected and analyzed in 111 BC patients, 42 DCIS patients and 39 healthy women by TaqMan real-time PCR. Identification of exosomes was performed by Western blot. The levels of exosomal miR-16 were higher in plasma of BC (p = 0.034) and DCIS (p = 0.047) patients than healthy women, and were associated with estrogen (p = 0.004) and progesterone (p = 0.008) receptor status. Particularly, in estrogen-positive patients miR-16 was significantly enriched in exosomes (p = 0.0001). Lower levels of exosomal miR-30b were associated with recurrence (p = 0.034). Exosomal miR-93 was upregulated in DCIS patients (p = 0.001). Our findings suggest that different signatures of miR-16, miR-30b and miR-93 in exosomes from BC and DCIS patients are associated with a particular biology of breast tumors.

Highlights

Loading of microRNAs into exosomes that are involved in cellular communication is a selective process
We found that deregulated levels of exosomal miR-16, miR-30b and miR-93 were most significantly associated with breast cancer (BC) receptor status, BC recurrence and ductal carcinoma in situ (DCIS), respectively
Real-time PCR-based miRNA array cards containing 45 miRNAs were used to quantify miRNAs in exosomes derived from plasma samples of 32 BC patients, 8 DCIS patients and 8 healthy women

Summary

Introduction

Loading of microRNAs (miRNAs) into exosomes that are involved in cellular communication is a selective process. The levels of exosomal miR-16 were higher in plasma of BC (p = 0.034) and DCIS (p = 0.047) patients than healthy women, and were associated with estrogen (p = 0.004) and progesterone (p = 0.008) receptor status. MiRNAs are a family of evolutionary conserved, small non-coding RNA molecules consisting of approximately 22 nucleotides They inhibit gene expression post-transcriptionally by binding to the 3′ untranslated-region (3′UTR) of their target mRNAs. Gene silencing occurs through translational inhibition or cleavage of their target mRNAs7. Due to their binding affinity to hundreds of different mRNAs, miRNAs regulate numerous signal transduction pathways Among others they participate in development, differentiation, proliferation, tumor development and progression[8]. We found that deregulated levels of exosomal miR-16, miR-30b and miR-93 were most significantly associated with BC receptor status, BC recurrence and DCIS, respectively

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