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Micropeptide and medicament for treating cancer

A cancer treatment and drug technology, applied in the field of biomedicine, can solve the problem of undetermined biological function of circRNA

Active Publication Date: 2019-12-10
PEKING UNIV THIRD HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the biological functions of most circRNAs remain undetermined

Method used

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  • Micropeptide and medicament for treating cancer
  • Micropeptide and medicament for treating cancer
  • Micropeptide and medicament for treating cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] See Figure 1A to Figure 1D , Effect of ectopic expression of micropeptide CORO1C-47aa on proliferation of EC cells.

[0058] Construction of EC cells cloned by circ-0000437OE vector and IRES mutant vector: The inventors cloned the full-length or mutated circ-0000437IRES sequence between the Rluc and Luc reporter genes to form two sets of vectors for comparing the high and low activity of Luc / Rluc. Then, the circ-0000437OE vector and the IRES mutation vector were transfected into EC cells (HEC-1-B, Ishikawa) to form EC cells that could overexpress the circ-0000437 vector and the IRES mutation. In order to determine whether the in-frame ATG codon of CORO1C-47aa can promote the initiation of translation, the inventors constructed an ORF mutation expression vector (in which the initiation codon ATGGTG has been mutated to ATTGTT) and FLAG tagged to the C-terminus of CORO1C-47aa. CORO1C-47aa-FLAG was detectable in cells transfected with the circ-0000437OE vector but not in c...

Embodiment 2

[0061] See Figure 2A to Figure 2J , This example studies the effects of micropeptide CORO1C-47aa on the proliferation, migration and differentiation of HUVEC cells. The inventors cultured HUVEC cells in the conditioned medium of HEC-1-B and Ishikawa cells transfected with CORO1C-47aa overexpression and IRES mutation. Such as Figure 2A As shown, the results of the HUVEC cell proliferation assay showed that the HUVEC cell proliferation in the CORO1C-47aa OE group was significantly reduced. To explore the effect of overexpression of CORO1C-47aa on HUVEC cell migration, the inventors used HUVEC cells cultured in conditioned medium for wound healing assay and Transwell. Such as Figure 2B and Figure 2C As shown, both the wound healing assay and Transwell demonstrated that the migration ability of HUVEC cells was significantly inhibited by the overexpression of CORO1C-47aa, while there was no significant difference between the IRES mutant group and the empty vector transfecti...

Embodiment 3

[0063] See image 3 , the expression of circ-0000437 is significantly different between endometrial cancer and adjacent tumors. The inventors used RT-qPCR assays to detect a total of 198 paired EC samples and matched EC samples in eastern China (Suzhou) and northern China (Beijing). Levels of circ-0000437 in noncancerous tissues. circ-0000437 was expressed at higher levels in paracancerous tissues compared with matched cancer tissues.

[0064] In summary: From the perspective of peptides encoded by circRNA at the translation level, the present invention studies the effect of peptides on neovascularization at the initial stage of endometrial cancer, and proves the important role of peptides in endometrial cancer. In view of the fact that the micropeptide CORO1C-47aa competes with the ARNTPAS-B domain, blocking the binding of TACC3 to its ligand PAS-B, resulting in the enrichment of HIF1 near the HRE promoter of VEGF and inhibiting its gene expression, so as to achieve the trea...

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Abstract

The invention relates to an application of a micropeptide CORO1C-47aa in treatment of cancer. From a perspective of translation-level cirRNA-encoded peptide, effect of the peptide on angiogenesis in an initial stage of endometrial cancer is studied, and through the treatment with the targeting micropeptide CORO1C-47aa, the micropeptide CORO1C-47aa competitively binds to a structural domain of ARNTYPAS-B to block binding of TACC3 and a ligand thereof PAS-B, resulting in accumulation of HIF1 near a HRE promoter of VEGF and thereby inhibiting gene expression. In vitro and in vivo experiments prove that the micropeptide CORO1C-47aa can obviously inhibit angiogenesis in the initial stage of endometrial cancer, and has clinical application value to endometrial cancer.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, in particular to the application of a micropeptide CORO1C-47aa in the treatment of cancer. Background technique [0002] Endometrial cancer (EC) is the fifth most common malignancy in women worldwide, accounting for 1-2% of all cancer deaths. Risk factors for developing EC include age, socioeconomic status, and factors associated with excess estrogen exposure, diabetes, or hypertension, but little is known about genetic risk factors for this disease. [0003] Noncoding RNAs (ncRNAs) represent the majority of transcripts in cells and are often involved in the development of EC. Circular RNAs (circRNAs) are a new class of ubiquitous ncRNAs that often regulate gene expression in mammals. CircRNAs are closed RNA transcripts generated by back-splicing of a single pre-mRNA, and the expression of circRNAs is often highly conserved across species. In recent years, most of the reported circRNAs hav...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/47A61K38/17A61P35/00
CPCA61K38/00A61P35/00C07K14/4703
Inventor 李华蔡雨晗
Owner PEKING UNIV THIRD HOSPITAL
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