Small Nuclear RNAs (U1, U2, U5) in Tumor-Educated Platelets Are Downregulated and Act as Promising Biomarkers in Lung Cancer.

Xiaohan Dong,Li Xie,Xianrang Song,Limin Niu,Yajing Zhao,Miao Yu,Xingguo Song,Shanshan Ding,Linlin Xue

doi:10.3389/fonc.2020.01627

Abstract

BackgroundSmall nuclear RNA (snRNA) levels are extremely variable across a wide range of biological conditions. SnRNAs could potentially regulate alternative splicing to drive genetic, dysplastic and neoplastic disease, which might be the main reason for mRNA profile alteration in tumor educated platelets (TEPs).MethodsPlatelets were isolated from the plasma of lung cancer patients and healthy donors by low-speed centrifugation and subjected to RNA isolation. SnRNA U1, U2, U5 levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were isolated by ultracentrifugation and identified by qNano.ResultsTEP U1, U2, U5 levels were significantly decreased in patients with lung cancer as well as with early stage patients, their downregulation was correlated with lung cancer progression, possessing favorable diagnostic efficiency. More importantly, TEP U1, U2 and U5 levels were closely correlated between paired exosomes and TEP from treated patients but not from untreated ones, and U1, U5 but not U2 in platelets were elevated by apo-exosomes.ConclusionTumor educated platelet small nuclear RNAs are downregulated and act as promising biomarkers in lung cancer.

Highlights

Small nuclear RNA levels are extremely variable across a wide range of biological conditions
We found that tumor educated platelet (TEP) U1, U2, U5 were significantly downregulated in lung cancer patients compared with those in healthy controls, possessing with the favorable diagnostic efficiency
To screen out the differential Small nuclear RNA (snRNA) expression levels in lung cancer, 10 snRNAs expression including U1, U2, U4, U5, U6, U7, U8, U12, U4ATAC and U6ATAC was detected in TEPs from 48 healthy donors and 48 lung cancer patients

Summary

Introduction

Small nuclear RNA (snRNA) levels are extremely variable across a wide range of biological conditions. SnRNAs could potentially regulate alternative splicing to drive genetic, dysplastic and neoplastic disease, which might be the main reason for mRNA profile alteration in tumor educated platelets (TEPs). Platelets, originating as anucleate cytoplasts from megakaryocytes [3], play crucial roles in hemostasis, and in systemic and local responses to the presence of cancer [4], thereby sequestering tumor-specified biomolecules including RNA transcripts and proteins, as well as altering their spliced RNA profiles, called “tumor educated platelets (TEPs)” [5]. TEPs emerged as non-invasive biomarker source for cancer detection and progression monitoring including colorectal carcinoma (CRC) [6], glioblastoma [7], non–small cell lung cancer (NSCLC) [8], prostate cancer [9] and etc., due to their significantly altered RNA profiles. Due to the lifespan of 7–10 days and the structure of platelet membrane, tumor-specified biosources and biomolecules are enriched in the TEPs and protected from circulating RNAs, and TEP RNA analysis is capable to reflect tumor bioactivity up-to-date, intensively, and dynamically

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