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CN-122011150-A - Polypeptide SPIRM and application thereof

CN122011150ACN 122011150 ACN122011150 ACN 122011150ACN-122011150-A

Abstract

The invention discloses a polypeptide SPIRM and application thereof. The invention discovers that LNCRNA VPS D1-AS1 has coding capability, contains a small open reading frame of 105bp, has a nucleotide sequence shown AS a sequence table SEQ ID NO. 2, can translate a novel polypeptide (named SPIRM) with a length of 34 amino acids, and has an amino acid sequence of a coding protein shown AS the sequence table SEQ ID NO. 1. The expression level of the polypeptide SPIRM can be used as a novel biomarker to help diagnosis of malignant tumors including kidney cancer, brain glioma, liver cancer, thyroid cancer or adrenocortical cancer, and the polypeptide SPIRM can be used as a potential drug for treating the malignant tumors, thereby providing a novel thought and prospect for development of novel antitumor drugs.

Inventors

  • LI MENGWEI
  • ZHANG CONGYI
  • CAI WENQIU
  • ZHUANG JIAJIE
  • YU NA

Assignees

  • 中国药科大学

Dates

Publication Date
20260512
Application Date
20241106

Claims (10)

  1. 1. Polypeptide SPIRM, which is characterized in that the amino acid sequence is shown in SEQ ID NO. 1.
  2. 2. A nucleic acid encoding the polypeptide SPIRM of claim 1, preferably having the nucleotide sequence shown in SEQ ID No. 2.
  3. 3. A recombinant expression vector comprising the nucleic acid of claim 2 or 3, and a lentivirus.
  4. 4. The PCR primer for specifically amplifying the nucleic acid of claim 2, wherein the PCR primer is preferably an upstream primer shown as SEQ ID NO.3 and a downstream primer shown as SEQ ID NO. 4.
  5. 5. Use of a substance for detecting the polypeptide SPIRM of claim 1 or the nucleic acid of claim 2 for the preparation of a tumor-assisted diagnostic reagent, preferably renal carcinoma, glioma, liver carcinoma, thyroid carcinoma and/or adrenocortical carcinoma.
  6. 6. The use according to claim 5, wherein the substance for detecting the polypeptide SPIRM according to claim 1 is an antibody specific for the polypeptide SPIRM and the substance for detecting the nucleic acid according to claim 2 is a PCR primer for specifically amplifying the nucleic acid according to claim 2 according to claim 4.
  7. 7. The use of the polypeptide SPIRM as claimed in claim 1 for the preparation of a medicament for the prophylaxis and/or treatment of tumors, preferably renal carcinoma, glioma, liver carcinoma, thyroid carcinoma and/or adrenocortical carcinoma.
  8. 8. The recombinant expression vector and the lentivirus of claim 3 are used for preparing medicaments for preventing and/or treating tumors, wherein the tumors are preferably kidney cancer, brain glioma, liver cancer, thyroid cancer and/or adrenocortical cancer.
  9. 9. A pharmaceutical composition for preventing or treating a tumor comprising the polypeptide SPIRM of claim 1 or comprising the recombinant expression vector of claim 3, a lentivirus, and pharmaceutically acceptable carriers thereof.
  10. 10. A tumor auxiliary diagnosis kit, which is characterized in that the kit contains the PCR primer of claim 4.

Description

Polypeptide SPIRM and application thereof Technical Field The invention belongs to the field of biological medicine, and relates to a polypeptide SPIRM and application thereof. Background The human genome comprises protein coding and non-coding regions, with only <2% of the regions being annotated as protein coding regions. The rapid development of high throughput and proteomics technology has led to a more extensive study of both the genome and its transcripts and the corresponding proteins. Recent studies have shown that the boundaries between encoded and non-encoded transcripts are less well defined. Translation of the protein starts at the start codon and ends at the stop codon of the open reading frame (open READING FRAMES, ORF) in the mRNA. Most algorithms for predicting ORFs have a minimum of 100 amino acids due to limitations of conventional computer algorithms. This standard allows many non-coding RNAs (non conding RNAs, ncrnas) to be misannotated, with the ORF of these ncrnas being smaller than the traditional threshold, we define a small open reading frame (small openreading frames, sORFs). More and more studies have shown that certain ncrnas can encode small proteins or micro-peptides. The micro peptide (Micropeptide) is a functional polypeptide which is derived from sORF, has in vivo translation capability and has the length of less than 100 amino acids, and has wide physiological and pathophysiological functions, including regulating embryo development, regulating the occurrence and development of tumors, regulating the development of muscles and the like. On the basis of high throughput sequencing, extensive research is also being undertaken for human related micro-peptides, many of which are found to be associated with tumors. Huang et al found that the micro peptide HOXB AS3 encoded by lncRNA HOXB AS3, and studied HOXBAS that can inhibit the growth of colon cancer (CRC), HOXBAS was the first functional micro peptide found to play a role in cancer. Guo et al found the cancer suppressing micro peptide CIP2A BPBP (cancerous inhibitor ofPP2A cancer inhibitory factor bindingpeptide) using ribosomal sequencing (Ribosome sequencing, ribo seq) and RNA sequencing (RNA sequence, RNA seq). Studies have shown that competitive binding of CIP2ABP to CIP2A releases the cancer suppressing factor PP2A, inactivating the PI 3K/AKT/nfkb pathway, resulting in reduced expression levels of matrix metalloproteinase 2 (matrix metallopeptidase, mmp 2), matrix metalloproteinase 9 (matrixmetallopeptidase, mmp 9), and Snail, thereby inhibiting invasion and metastasis of breast cancer. In addition, the inventor establishes a technical platform for finding the micro-peptide by utilizing means of transcriptome sequencing data analysis, proteomics, CRISPR/cas9 gene editing, in vivo translation and the like, finds a brand-new endogenous micro-peptide MIAC (micropeptide inhibiting actin cytoskeleton) coded by lncRNA in head and neck squamous cell carcinoma for the first time, and proves that the novel endogenous micro-peptide MIAC (micropeptide inhibiting actin cytoskeleton) is directly combined with aquaporin AQP2 to regulate and control the expression of Sept2 and ITGB4, so that the occurrence and development of the head and neck squamous cell carcinoma are inhibited. Tumor-associated micro peptides are also found in various cancers such as liver cancer and rectal cancer, for example SMIM30、MPM(micropeptide in mitochondria)、ASAP(ATP synthase-associatedpeptide)、APPLE(apeptide located in ER). The proportion of non-coding RNA in human genome exceeds 90%, but the novel micro peptide is less, so that the novel polypeptide is discovered by combining multiple groups of chemical platforms and bioinformatics technologies, and the systematic research on the functions and mechanisms of the novel polypeptide is an important direction for developing original polypeptide medicaments. However, the existing novel micro-peptide discovery mainly focuses on specific functional research in a specific tumor, but lacks of a cancer-making analysis, and the novel micro-peptide discovery plays a role in common regulation and control in different cancers, so that more new choices are provided for tumor diagnosis and treatment. Disclosure of Invention The invention takes the whole transcriptome sequencing data of a kidney cancer sample as a research basis, and obtains a novel polypeptide SPIRM encoded by lncRNA through combining with translation histology and proteomics analysis and in vivo translation level detection, and analyzes the pan-cancer species to determine the importance and application value of SPIRM in various tumors. Based on the above, the present project provides the following technical solutions: It is a first object of the present invention to provide a novel polypeptide SPIRM. Preferably, the polypeptide is obtained by chemical synthesis or biosynthesis. It is a second object of the present invention to provide a nucleic acid mole