CN-122005799-A - Application of TRMT A serving as target spot in preparation of medicine for preventing or treating benign prostatic hyperplasia

Abstract

The invention provides an application of TRMT A serving as a target in preparing a medicament for preventing or treating benign prostatic hyperplasia. According to the invention, through shRNA specific targeting TRMT A, pathogenic signals are blocked from posttranscriptional level, accurate intervention on benign prostatic hyperplasia is realized, androgen passage is completely not relied on, serious side effects such as unavoidable sexual dysfunction of traditional medicines are fundamentally avoided, and the life quality of patients is remarkably improved.

Inventors

• MEI HONGBING
• LIU YUHAN
• YU LIBO

Assignees

• 深圳市第二人民医院(深圳市转化医学研究院)

Dates

Publication Date

20260512

Application Date

20260114

Claims (10)

1. 1. Use of TRMT a as a target in the manufacture of a medicament for the prevention or treatment of benign prostatic hyperplasia.
2. 2. The use according to claim 1, wherein the benign prostatic hyperplasia is early, medium or progressive benign prostatic hyperplasia.
3. 3. The use of claim 1, wherein the agent reduces the m 1 a methylation level of the tRNA, inhibits the efficiency of cellular overall protein translation to prevent or treat benign prostatic hyperplasia.
4. 4. The use of claim 1, wherein the medicament comprises a TRMT a inhibitor.
5. 5. The use of claim 4, wherein the TRMT a inhibitor is a shRNA, siRNA, miRNA mimetic, an antisense oligonucleotide, a CRISPR-Cas gene editing system, an aptamer, or a neutralizing antibody.
6. 6. The use according to claim 5, wherein the TRMT a inhibitor is an shRNA having the nucleotide sequence shown in SEQ ID No.1 or 2.
7. 7. The use of claim 5, wherein the TRMT a inhibitor is delivered to the prostate tissue by a viral vector or a non-viral delivery system.
8. 8. The use according to claim 7, wherein the viral vector is an adeno-associated virus, a lentivirus or an adenovirus.
9. 9. The use of claim 7, wherein the non-viral delivery system is a liposome, a polymeric nanoparticle, an inorganic nanocarrier, or an exosome.
10. 10. The use according to claim 1, wherein the medicament is administered by transurethral prostate infusion, ultrasound guided injection or slow release implants.

Description

Application of TRMT A serving as target spot in preparation of medicine for preventing or treating benign prostatic hyperplasia Technical Field The invention relates to the technical field of biological medicines, in particular to an application of TRMT A serving as a target in preparing a medicine for preventing or treating benign prostatic hyperplasia. Background Benign Prostatic Hyperplasia (BPH) is the most important cause of urination dysfunction in middle-aged and elderly men, and core pathology is changed into uncontrolled proliferation of prostatic transitional zone epithelium and interstitial cells, which causes pathological increase of gland volume, presses urethra, causes bladder outlet obstruction (bo), further causes frequent urination, urgent urination, urinary retention and even kidney function damage, thereby seriously affecting life quality of patients. Currently, the clinical treatment of BPH relies mainly on alpha-receptor blockers (e.g. tamsulosin) and 5 alpha-reductase inhibitors (e.g. finasteride). However, these therapies have significant limitations in that alpha-blockers only relieve symptoms, cannot reduce prostate volume, cannot delay disease progression, and 5 alpha-reductase inhibitors can reduce glands, but their mechanism of action depends on hormonal blockade, and are slow to take 3-6 months, and have serious side effects such as hyposexuality, erectile dysfunction, ejaculation abnormality and drug resistance, and are ineffective against hormone-independent hyperplasia. Therefore, there is an urgent need for a novel therapeutic target that does not rely on the androgen pathway, can rapidly induce apoptosis in prostate hyperplasia cells, and simultaneously reduces side effects. The apparent transcriptome intervention therapy which is independent of hormone has the advantages of no influence on the whole body endocrine level, strong targeting property and the like compared with the traditional hormone therapy by regulating the translation efficiency of pathogenic genes from the source head, thereby becoming a promising new therapeutic direction of BPH. Among them, the N1-methyl adenosine (m 1 A) modification of tRNA has been shown to be a core switch that regulates the rate of protein synthesis in key signal pathways (e.g., TGF-beta pathway). TGF-beta signaling is a key factor driving prostatic epithelial proliferation and interstitial fibrosis (EMT), but there is currently no effective means to treat BPH by interfering with its translational regulatory mechanisms. Disclosure of Invention Aiming at the defects of side effects and drug resistance bottlenecks of hormone blocking therapy in the prior art, the invention provides application of TRMT A serving as a target point in preparing a medicament for preventing or treating benign prostatic hyperplasia. The invention reveals TRMT A for the first time that the m 1 A modification of tRNA-Leu-CAA is maintained, and the translation efficiency of key proteins of TGF-beta signal channels is specifically enhanced, so that a novel mechanism of prostatic hyperplasia and fibrosis is driven. The invention realizes the intervention of the channel through TRMT A specific interfering RNA (shRNA), can block tRNA m 1 A modification from the source, inhibit abnormal activation of TGF-beta signal, effectively inhibit proliferation and fibrosis process of prostate cells on the premise of keeping the sexual function of patients, and realize the treatment of benign prostatic hyperplasia. The invention provides an application of TRMT A serving as a target in preparing a medicament for preventing or treating benign prostatic hyperplasia. In some embodiments, the benign prostatic hyperplasia is early, medium or progressive benign prostatic hyperplasia. In some embodiments, the agent reduces the m 1 a methylation level of the tRNA, inhibits the efficiency of cellular overall protein translation to prevent or treat benign prostatic hyperplasia. In some embodiments, the medicament comprises TRMT a inhibitor. In some embodiments, the TRMT a inhibitor is a shRNA, siRNA, miRNA mimetic, an antisense oligonucleotide, a CRISPR-Cas gene editing system, an aptamer, or a neutralizing antibody. In some embodiments, the TRMT a inhibitor is an shRNA having a nucleotide sequence as set forth in SEQ ID No.1 or 2. In some embodiments, the TRMT a inhibitor is delivered to the prostate tissue by a viral vector or a non-viral delivery system. In some embodiments, the viral vector is an adeno-associated virus, a lentivirus, or an adenovirus. In some embodiments, the non-viral delivery system is a liposome, a polymeric nanoparticle, an inorganic nanocarrier, or an exosome. In some embodiments, the drug may be administered via transurethral prostate infusion, ultrasound guided injection, or slow release implants. In conclusion, compared with the prior art, the invention achieves the following technical effects: (1) The invention initiates a 'translation blocking' strategy, a