Post-Transcriptional Expression Control in Platelet Biogenesis and Function

Neu, Carolin; Gutschner, Tony; Haemmerle, Monika

doi:10.3390/ijms21207614

Cited by 21 publications

(15 citation statements)

References 176 publications

(216 reference statements)

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“…Next to the already established RNA-based biomarkers such as mRNAs and microRNAs, the circRNAs are emerging as a novel biomarker candidate. Platelets have a higher circRNA content, compared with their progenitor cells, megakaryocytes, or other hematopoietic cells [ 27 , 34 , 35 ]. The enrichment of circRNAs may be due to the degradation of linear RNAs occurring in platelets [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…Blood platelets are small anucleate cells that originate from megakaryocytes and are the second most abundant cells in peripheral blood [ 25 ]. Platelets harbor several types of RNA (both coding and non-coding) that are inherited from megakaryocytes or directly and indirectly transfer from other cells [ 26 , 27 , 28 ]. The nucleic acid content of platelets can be affected or “educated” by their environment, including a primary tumor, by the passage of biomolecules or signaling that modified their RNA content [ 26 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

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The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer

D’Ambrosi

Visser

Antunes-Ferreira

et al. 2021

Cancers

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Tumor-educated Platelets (TEPs) have emerged as rich biosources of cancer-related RNA profiles in liquid biopsies applicable for cancer detection. Although human blood platelets have been found to be enriched in circular RNA (circRNA), no studies have investigated the potential of circRNA as platelet-derived biomarkers for cancer. In this proof-of-concept study, we examine whether the circRNA signature of blood platelets can be used as a liquid biopsy biomarker for the detection of non-small cell lung cancer (NSCLC). We analyzed the total RNA, extracted from the platelet samples collected from NSCLC patients and asymptomatic individuals, using RNA sequencing (RNA-Seq). Identification and quantification of known and novel circRNAs were performed using the accurate CircRNA finder suite (ACFS), followed by the differential transcript expression analysis using a modified version of our thromboSeq software. Out of 4732 detected circRNAs, we identified 411 circRNAs that are significantly (p-value < 0.05) differentially expressed between asymptomatic individuals and NSCLC patients. Using the false discovery rate (FDR) of 0.05 as cutoff, we selected the nuclear receptor-interacting protein 1 (NRIP1) circRNA (circNRIP1) as a potential biomarker candidate for further validation by reverse transcription–quantitative PCR (RT-qPCR). This analysis was performed on an independent cohort of platelet samples. The RT-qPCR results confirmed the RNA-Seq data analysis, with significant downregulation of circNRIP1 in platelets derived from NSCLC patients. Our findings suggest that circRNAs found in blood platelets may hold diagnostic biomarkers potential for the detection of NSCLC using liquid biopsies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer

D’Ambrosi

Visser

Antunes-Ferreira

et al. 2021

Cancers

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“…LncRNAs have also been reported to play critical roles in the immune response to cancer [ 49 , 50 ]. We identified 62 differentially expressed lncRNAs correlated with immune infiltration by comparing lncRNA expression levels in the two different immune infiltration groups.…”

Section: Discussionmentioning

confidence: 99%

Construction of a Prognostic Gene Signature Associated with Immune Infiltration in Glioma: A Comprehensive Analysis Based on the CGGA

Gong

Liu

Xiong

et al. 2021

Journal of Oncology

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Background. Tumor microenvironment (TME) is closely related to the progression of glioma and the therapeutic effect of drugs on this cancer. The aim of this study was to develop a signature associated with the tumor immune microenvironment using machine learning. Methods. We downloaded the transcriptomic and clinical data of glioma patients from the Chinese Glioma Genome Atlas (CGGA) databases (mRNAseq_693). The single-sample Gene Set Enrichment Analysis (ssGSEA) database was used to quantify the relative abundance of immune cells. We divided patients into two different infiltration groups via unsupervised clustering analysis of immune cells and then selected differentially expressed genes (DEGs) between the two groups. Survival-related genes were determined using Cox regression analysis. We next randomly divided patients into a training set and a testing set at a ratio of 7 : 3. By integrating the DEGs into least absolute shrinkage and selection operator (LASSO) regression analysis in the training set, we were able to construct a 15-gene signature, which was validated in the testing and total sets. We further validated the signature in the mRNAseq_325 dataset of CGGA. Results. We identified 74 DEGs associated with tumor immune infiltration, 70 of which were significantly associated with overall survival (OS). An immune-related gene signature was established, consisting of 15 key genes: adenosine triphosphate (ATP)-binding cassette subfamily C member 3 (ABCC3), collagen type IV alpha 1 chain (COL4A1), podoplanin (PDPN), annexin A1 (ANXA1), COL4A2, insulin-like growth factor binding protein 2 (IGFBP2), serpin family A member 3 (SERPINA3), CXXC-type zinc finger protein 11 (CXXC11), junctophilin 3 (JPH3), secretogranin III (SCG3), secreted protein acidic and rich in cysteine (SPARC)-related modular calcium-binding protein 1 (SMOC1), Cluster of Differentiation 14 (CD14), COL1A1, S100 calcium-binding protein A4 (S100A4), and transforming growth factor beta 1 (TGF-β1). The OS of patients in the high-risk group was worse than that of patients in the low-risk group. GSEA showed that interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT3) signaling, interferon gamma (IFN-γ) response, angiogenesis, and coagulation were more highly enriched in the high-risk group and that oxidative phosphorylation was more highly enriched in the low-risk group. Conclusion. We constructed a stable gene signature associated with immune infiltration to predict the survival rates of glioma patients.

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“…Platelets inherit RNA pool, including pre-miRNAs, from their parent megakaryocytes ( 30 , 31 ). These RNAs become important sources of platelet miRNA as they may be processed into mature miRNA by functional Dicer as templates ( 22 , 27 ). Besides, miRNAs can bidirectionally transfer between platelets and the surrounding environment ( 32 ).…”

Section: Introductionmentioning

confidence: 99%

Insights Into Platelet-Derived MicroRNAs in Cardiovascular and Oncologic Diseases: Potential Predictor and Therapeutic Target

Leng

Ding

Dai

et al. 2022

Front. Cardiovasc. Med.

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Non-communicable diseases (NCDs), represented by cardiovascular diseases and cancer, have been the leading cause of death globally. Improvements in mortality from cardiovascular (CV) diseases (decrease of 14%/100,000, United States) or cancers (increase 7.5%/100,000, United States) seem unsatisfactory during the past two decades, and so the search for innovative and accurate biomarkers of early diagnosis and prevention, and novel treatment strategies is a valuable clinical and economic endeavor. Both tumors and cardiovascular system are rich in angiological systems that maintain material exchange, signal transduction and distant regulation. This pattern determines that they are strongly influenced by circulating substances, such as glycolipid metabolism, inflammatory homeostasis and cyclic non-coding RNA and so forth. Platelets, a group of small anucleated cells, inherit many mature proteins, mRNAs, and non-coding RNAs from their parent megakaryocytes during gradual formation and manifest important roles in inflammation, angiogenesis, atherosclerosis, stroke, myocardial infarction, diabetes, cancer, and many other diseases apart from its classical function in hemostasis. MicroRNAs (miRNAs) are a class of non-coding RNAs containing ∼22 nucleotides that participate in many key cellular processes by pairing with mRNAs at partially complementary binding sites for post-transcriptional regulation of gene expression. Platelets contain fully functional miRNA processors in their microvesicles and are able to transport their miRNAs to neighboring cells and regulate their gene expression. Therefore, the importance of platelet-derived miRNAs for the human health is of increasing interest. Here, we will elaborate systematically the roles of platelet-derived miRNAs in cardiovascular disease and cancer in the hope of providing clinicians with new ideas for early diagnosis and therapeutic strategies.

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Post-Transcriptional Expression Control in Platelet Biogenesis and Function

Cited by 21 publications

References 176 publications

The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer

The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer

Construction of a Prognostic Gene Signature Associated with Immune Infiltration in Glioma: A Comprehensive Analysis Based on the CGGA

Insights Into Platelet-Derived MicroRNAs in Cardiovascular and Oncologic Diseases: Potential Predictor and Therapeutic Target

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