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A kind of circpten1 for tumor therapy target and diagnostic biomarker and its application

A tumor and tumor migration technology, applied in the biological field, can solve problems such as unclear specific functions

Active Publication Date: 2022-04-01
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But in general, the specific role of most circRNAs in the process and pathogenesis of colorectal cancer remains unclear

Method used

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  • A kind of circpten1 for tumor therapy target and diagnostic biomarker and its application
  • A kind of circpten1 for tumor therapy target and diagnostic biomarker and its application
  • A kind of circpten1 for tumor therapy target and diagnostic biomarker and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Discovery and identification of circular RNA (circPTEN1) derived from PTEN gene

[0055] In this implementation case, the existence of circular RNA (circPTEN) derived from the PTEN gene was determined by using biological information means combined with PCR amplification technology and its biological characteristics were identified. The specific content is as follows:

[0056] 1. Discovery of circular RNA (circPTEN) derived from PTEN gene

[0057] Using the circBase (http: / / www.circbase.org) database analysis, it was found that the PTEN gene can be spliced ​​to form 8 kinds of circRNAs, namely hsa_circ_0002232, hsa_circ_0002934, hsa_circ_0003058, hsa_circ_0019058, hsa_circ_0019059, hsa_circ_0019060, hsa_4circ_3 and 0hsa_4circ_4.

[0058] Different from the traditional linear splicing of PTEN mRNA, hsa_circ_0002232 is encoded by the PTEN gene (chr10:89624210-89693008) The second half of the first exon and the 2nd, 3rd, 4th, 5th exons through reverse spliced, and its matu...

Embodiment 2

[0094] Expression of circPTEN in colorectal cancer tissues

[0095] In this implementation case, the use of qRT-PCR and FISH experiments revealed that the expression of circPTEN in colorectal cancer tissues was down-regulated and related to the clinicopathological indicators and prognosis of patients. The details are as follows:

[0096] 1. qRT-PCR and FISH experiments reveal that circPTEN is down-regulated in colorectal cancer tissues

[0097] 1.1 qRT-PCR revealed that the expression of circPTEN was decreased in colorectal cancer tissues. The previous identification experiments of circPTEN revealed that circPTEN is an abundant and stable circRNA expressed in colorectal cancer produced by PTEN through back splicing. In order to further explore the relationship between circPTEN and colorectal cancer, the expression level of circPTEN was detected by qRT-PCR in 150 pairs of fresh colorectal cancer tissues and their paired paracancerous tissues (the primer sequences were SEQ ID N...

Embodiment 3

[0109] In this implementation case, experiments such as RNApulldown, RIP, Western blot, and qRT-PCR revealed that the expression level of circPTEN1 is regulated by EIF4A3, and the details are as follows:

[0110] In order to explore why the expression level of circPTEN1 is down-regulated in colorectal cancer tissues, that is, to explore the specific factors that regulate the expression level of circPTEN1, we first analyzed the formation mechanism of circRNA. The formation mechanism of circRNA mainly includes intron pairing-driven circularization and RBP-driven circularization, that is, the upstream and downstream flanking introns of circRNA contain Alu sequences with reverse complementary sequences or RBP is combined in the flanking introns, both It can regulate the splicing and circularization of circRNA. Many RBPs (such as QKI, FUS, and ADAR1, etc.) can bind to the intron sequences around the circular exon, thereby promoting or inhibiting the circularization of circRNA. How...

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Abstract

The invention provides a circPTEN1 used as a tumor treatment target and a diagnostic biomarker and its application, belonging to the field of biotechnology. circPTEN1, which is used as a target for tumor therapy and a diagnostic biomarker, has a nucleotide sequence shown in SEQ ID NO: 1, and is a new circular RNA formed by reverse splicing of exons 1 to 5 of PTEN mRNA. High expression of circPTEN1 significantly inhibited the migration and invasion of colorectal cancer cells, the expression level of circPTEN1 was negatively correlated with lymph node metastasis and distant metastasis in colorectal cancer patients, and the prognosis of colorectal cancer patients with low expression of circPTEN1 was poor. Therefore, circPTEN1 is used as a tumor therapeutic target and diagnostic biomarker in tumor treatment, tumor diagnosis, and assessment of tumor prognosis, and provides new ideas and strategies for treatment-related drugs and diagnostic products.

Description

technical field [0001] The invention belongs to the technical field of biotechnology, and in particular relates to a circPTEN1 used as a tumor treatment target and a diagnostic biomarker and an application thereof. Background technique [0002] PTEN gene is one of the most frequently mutated tumor suppressor genes in human tumors, and its mutation or deletion is closely related to the occurrence and development of various human tumors. Previous studies have proved that PTEN protein can inhibit PI3K / Akt signaling cascade reaction by dephosphorylating and dephosphorylating PtdIns(3,4,5)P3, thereby controlling cell proliferation, invasion, and promoting cell apoptosis. In addition to its tumor suppressor function, PTEN gene also participates in various biological processes such as cell metabolism and antiviral innate immunity. In recent years, it has been found that, in addition to the traditional PTEN protein, the PTEN gene can encode three new subtypes of the N-terminally ex...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/113C12Q1/6886A61K31/7105A61P35/00A61P35/04
CPCC12N15/1135C12Q1/6886A61K31/7105A61P35/00A61P35/04C12Q2600/118C12Q2600/178C12Q2600/158C12N2310/532C12N2320/30
Inventor 尹玉新梁会郑林
Owner PEKING UNIV
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