Promises and Pitfalls of microRNAs as Biomarkers of Heart Failure

Review Article

Austin J Biotechnol Bioeng. 2024; 11(2): 1133.

Promises and Pitfalls of microRNAs as Biomarkers of Heart Failure

Raissi-Dehkordi NA¹; Raissi-Dehkordi NE¹; Farjoo MH²*

1Department of Pharmacology, Shahid Beheshti University of Medical Sciences, Iran

2Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Iran

*Corresponding author: Farjoo MH Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Daneshjoo Blvd, Velenjak, P.O. Box: 19835355, Tehran-Iran. Tel: 23872539; Fax: 22439969 Email: m.farjoo@sbmu.ac.ir

Received: April 29, 2024 Accepted: May 24, 2024 Published: May 31, 2024

Abstract

Background: MicroRNAs (miRNAs) are important non-coding molecules with regulatory roles in gene expression. In the past few years, miRNAs have arisen as apt candidates to assist with the diagnosis, prognosis and monitoring of several diseases. Cardiovascular pathologies have emerged as a particularly interesting field for miRNAs as markers, as it appears that the pathophysiological changes following heart failure lead to measurable alterations in circulating miRNA levels.

Contents: In the present review, we explore the value, sensitivity and specificity of circulating miRNAs in diagnosis and prognosis of heart failure as reported in the literature, and discuss the underlying factors that currently prevent circulating miRNAs from becoming true clinical markers. In spite of the numerous attempts in identification and administration of cardiac miRNA markers, relatively small progress has been made in the application of these markers in clinical settings.

Small study populations and methodological differences, among other possible etiologies, have resulted in little reproducibility among studies.

Conclusion: Despite the encouraging preliminary results, considerable challenges, mainly concerning standardization, have thus far prevented miRNAs from approximating the validity of established biomarkers that are routinely used in clinics, let alone surpassing them. To conclude, rigorous methodology and universally standardized protocols prior to, and during miRNA analysis are required to warrant reproducible, validated and reliable results which will lead to clinical application of miRNA cardiac biomarkers.

Keywords: microRNA; Heart failure; Diagnosis; Prognosis; Biomarker

Abbreviations: miRNAs: MicroRNAs; RISC: RNA-Induced Silencing Complex; MI: myocardial infarction; HF: Heart Failure; BNP: B-type Natriuretic Peptide; NT-proBNP: N-Terminal pro–B-type Natriuretic Peptide; NYHA: New York Heart Association; RT-qPCR: Quantitative Reverse Transcription Polymerase Chain Reaction; LVEF: Left Ventricular Ejection Fraction; hs-cTnT: High-Sensitivity Cardiac Troponin T; AUC: Area Under the Curve; DOR: Diagnostic Odds Ratio; CI: Confidence Interval; HR: Hazard Ratio; RT-qPCR: Reverse Transcription Polymerase Chain Reaction; CHF: Congestive Heart Failure; ICM: Ischemic Cardiomyopathy; NICM: Non-Ischemic Cardiomyopathy; AHF: Acute HF; OR: Odds Ratio; CRT: Cardiac Resynchronization Therapy; SROC: Summary Receiver Operating Characteristic Curves Value; qPCR: quantitative PCR; NGS: Next Generation Sequencing.

Introduction

MicroRNAs (miRNAs) are short non-coding RNAs of around 22 nucleotides involved in post-transcriptional gene expression regulation. lin-4 miRNA, the first miRNA discovered in 1993 in a nematode, Caenorhabditis elegans, was involved in producing non-coding RNAs that controlled the development of C. elegans through regulating the expression of a protein, lin-14. Subsequently, another miRNA, let-7 was discovered in C. elegans, which was involved in developmental timing [1,2]. Let-7 was subsequently discovered in humans in 2000 [3] miRNA genes are transcribed by RNA polymerase II & III from primary miRNA into precursor miRNA and finally mature miRNA [4]. Primary miRNAs containing stem-loop structures are cleaved in the nucleus into precursor miRNAs by DGCR8, an RNase III enzyme. Precursor miRNAs are then exported into the cytoplasm by Exportin-5, where Dicer removes the terminal loop from the hairpin structure and creates a miRNA-miRNA duplex [5]. Following the unwinding of the duplex, Argonaute protein integrates one of the mature miRNA strands, the so-called guide strand, into RNA-Induced Silencing Complex (RISC), while the other strand, nominated passenger strand, is degraded in the cytoplasm. Subsequent binding of the guide strand and RISC to complementary mRNAs results in degradation or inhibition of translation [6]. A summary of miRNA biogenesis can be found in Figure 1.

Citation: Raissi-Dehkordi NA, Raissi-Dehkordi NE, Farjoo MH. Promises and Pitfalls of microRNAs as Biomarkers of Heart Failure. Austin J Biotechnol Bioeng. 2024; 11(2): 1133.