CN-121975930-A - Application of tsRNA-3025a as acute myocardial infarction prognosis marker and myocardial ischemia reperfusion injury treatment target

Abstract

The invention relates to an application of tsRNA-3025a as a prognosis marker for acute myocardial infarction and a target point for myocardial ischemia reperfusion injury treatment, wherein a DNA sequence corresponding to tsRNA-3025a is shown as SEQ ID NO. 1 and is 5'-ATCCTGCCGACTACGCCA-3'. In terms of prognosis, a test kit is provided for assessing the risk of heart failure and short-term adverse events in a patient by quantitatively detecting the tsRNA expression levels. In therapeutic aspects, there is provided the use of an antagomir inhibiting tsRNA-3025a function or expression in the manufacture of a medicament for the treatment of myocardial ischemia reperfusion injury, said antagomir being specifically chemically modified. The invention provides a novel biomarker for acute myocardial infarction prognosis risk stratification and an effective treatment strategy for preventing and treating myocardial ischemia reperfusion injury.

Inventors

• QIAN LINGMEI
• FENG ZEHAO
• ZHANG LI
• ZHANG HAN
• TANG KAIXUAN

Assignees

• 上海市同仁医院

Dates

Publication Date

20260505

Application Date

20251217

Claims (8)

1. 1. A kit for acute myocardial infarction prognosis is characterized by comprising a primer group for detecting tsRNA-3025a by stem-loop reverse transcription quantitative PCR, wherein the DNA sequence corresponding to tsRNA-3025a is shown as SEQ ID NO. 1: 5'-ATCCTGCCGACTACGCCA-3'.
2. 2. The kit of claim 1, wherein the primer set comprises: (a) The sequence of the reverse transcription stem-loop primer is shown as SEQ ID NO. 2; (b) The forward primer for PCR amplification has the sequence shown in SEQ ID NO. 3; (c) The sequence of the reverse primer for PCR amplification is shown as SEQ ID NO. 4.
3. 3. The kit of claim 1, wherein the prognosis is assessed for assessing the risk of heart failure in a patient following acute myocardial infarction. .
4. 4. The kit of claim 1, wherein the prognosis is assessed for the risk of a short-term adverse event in a patient following acute myocardial infarction.
5. 5. The kit of claim 1, further comprising detection primers for the internal reference gene U6 and the external reference gene cel-miR-39-3 p.
6. 6. Use of an agent that inhibits tsRNA-3025a function or expression in the manufacture of a medicament for the treatment of myocardial ischemia reperfusion injury.
7. 7. The use according to claim 6, wherein the agent is a single-stranded antagomir.
8. 8. The use according to claim 7, wherein the antagomir has a chemical modification of cholesterol at the 3 'end, phosphorothioate backbone modification between four nucleotides at the 3' end, phosphorothioate backbone modification between two nucleotides at the 5 'end, and full-chain 2' -O-methyl modification.

Description

Application of tsRNA-3025a as acute myocardial infarction prognosis marker and myocardial ischemia reperfusion injury treatment target Technical Field The invention relates to the technical field of biological medicines, in particular to an application of tsRNA-3025a as an acute myocardial infarction prognosis marker and a myocardial ischemia reperfusion injury treatment target. Background Coronary heart disease is one of the major health burdens worldwide. Acute Coronary Syndrome (ACS) is a serious clinical manifestation of coronary heart disease, mainly covering ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and Unstable Angina (UA). Among them, acute Myocardial Infarction (AMI) refers to a critical condition of myocardial cell necrosis caused by acute occlusion of coronary arteries. Percutaneous Coronary Intervention (PCI) is a critical recanalization strategy to restore myocardial perfusion and rescue dying myocardium, however, successful restoration of blood flow is often accompanied by Myocardial Ischemia Reperfusion Injury (MIRI), which can manifest as malignant arrhythmia, in-hospital cardiac arrest, or acute heart failure, significantly affecting the patient's recent prognosis and long-term quality of life. Thus, the search for novel biomarkers that can identify high-risk patients early, predict poor prognosis, and develop effective intervention strategies for reperfusion injury has become an urgent need for current clinical research. Non-coding RNAs play a critical regulatory role in cellular processes. In recent years, a new class of non-coding RNAs, the transfer RNA-derived small RNAs (tsrnas), has attracted attention. tsRNA are derived from the cleavage products of tRNA precursors or mature tRNA under specific conditions, and can be broadly divided into tRNA-derived stress-induced RNAs (tRNAs, about 31-40nt in length) and tRNA-derived fragments (tRNAs, similar in length to miRNAs) depending on their cleavage site and length. Studies have shown that part tsRNA can be involved in post-transcriptional gene silencing via the Argonaute (Ago) protein complex, showing potential as a diagnostic and prognostic biomarker in tumors, metabolic diseases, and neurodegenerative diseases. In the field of cardiovascular diseases, tiRNA-HUR has been shown to be involved in regulating the myocardial ischemia reperfusion injury process, and further studies have found that tiRNA-Met-CAT-002 exacerbates reperfusion-induced myocardial cell injury by affecting Bnip 3-mediated mitochondrial autophagy pathways. Autophagy is a key mechanism for maintaining stable intracellular environments, and its role in the various stages of ischemia/reperfusion remains controversial, with excessive or insufficient autophagic flow potentially affecting cardiomyocyte survival. Nevertheless, the current systematic study of tsRNA for acute myocardial infarction prognosis evaluation and as a target for reperfusion injury treatment is still relatively lacking, and the value of tsRNA in clinical transformation is still yet to be deeply explored. Disclosure of Invention The invention aims at overcoming the defects in the prior art and provides an application of tsRNA-3025a as an acute myocardial infarction prognosis marker and a myocardial ischemia reperfusion injury treatment target. In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: The first aspect provides a kit for acute myocardial infarction prognosis, which comprises a primer pair for detecting tsRNA-3025a, wherein a DNA sequence corresponding to tsRNA-3025a is shown as SEQ ID NO. 1: 5'-ATCCTGCCGACTACGCCA-3'. Further, the prognosis is assessed as assessing the risk of developing heart failure. Further, the prognosis is assessed for the risk of developing a short-term adverse event. Further, for stem loop reverse transcription quantitative PCR, the primer pair comprises a forward primer as shown in SEQ ID NO.2 and a reverse primer as shown in SEQ ID NO. 3. Further, for poly (A) tail reverse transcription quantitative PCR, the primer pair comprises a forward primer as shown in SEQ ID NO. 4 and a reverse primer as shown in SEQ ID NO. 5. Further, the kit also comprises detection primers of an internal reference gene U6 and an external reference gene cel-miR-39-3 p. In a second aspect, there is provided the use of an agent which inhibits tsRNA-3025a function or expression in the manufacture of a medicament for the treatment of myocardial ischemia reperfusion injury, the agent being a single-chain antagomir. Further, the antagomir has chemical modifications of 3 '-terminal cholesterol modification, phosphorothioate backbone modification between the four nucleotides at the 3' -terminal, phosphorothioate backbone modification between the two nucleotides at the 5 '-terminal, and full-chain 2' -O-methyl modification. Compared with the prior art, the invention has the following technical effects: The i