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CN-121971619-A - Application of ELK1 and LINC00839 genes in regulation and control of treatment effect of nasopharyngeal iron death inducer

CN121971619ACN 121971619 ACN121971619 ACN 121971619ACN-121971619-A

Abstract

The invention discloses an application of ELK1 and LINC00839 genes in regulating and controlling the treatment effect of an iron death inducer for nasopharyngeal carcinoma, and belongs to the technical field of genetic engineering. The invention discloses a key role of ELK1 gene and LINC00839 gene in regulating iron death sensitivity of nasopharyngeal carcinoma cells. Experiments prove that inhibiting the expression of ELK1 or LINC00839 can obviously improve the sensitivity of nasopharyngeal carcinoma cells to iron death inducers such as sorafenib, erastin and RSL3, and conversely, the over-expression of ELK1 or LINC00839 can obviously reduce the sensitivity of nasopharyngeal carcinoma cells to iron death. The invention provides definite targets and technical support for developing the medicine for overcoming the iron death resistance and enhancing the curative effect of the nasopharyngeal carcinoma, and provides a new solution for solving the treatment failure problem caused by the iron death resistance in the nasopharyngeal carcinoma.

Inventors

  • GUO ZHEN

Assignees

  • 长沙医学院

Dates

Publication Date
20260505
Application Date
20260209

Claims (10)

  1. 1. The application of a product for inhibiting the expression, activity or function of ELK1 gene or LINC00839 gene in preparing the medicine for improving the treatment effect of nasopharyngeal iron death inducer.
  2. 2. The use according to claim 1, wherein the product that inhibits the expression, activity or function of ELK1 gene comprises any one of the following: A1. Sgrnas targeting ELK1 genes; A2. shRNA targeting ELK1 gene; A3. siRNA targeting ELK1 gene; A4. miRNA targeting ELK1 gene; A5. Antisense oligonucleotide ASO of targeted ELK1 gene; A6. a blocker, antagonist or inhibitor targeting the ELK1 gene, inhibiting its expression, activity or function; A7. a plasmid vector, lentiviral vector, adenoviral vector, adeno-associated vector or sgRNA ribonucleoprotein complex comprising the sgRNA described in A1; A8. A plasmid vector, lentiviral vector, adenoviral vector or adenovirus-associated vector comprising the shRNA described in A2; A9. a plasmid vector, lentiviral vector, adenoviral vector or adenovirus-associated vector comprising the siRNA described in A3; A10. A plasmid vector, lentiviral vector, adenoviral vector or adenovirus-associated vector comprising the miRNA described in A4; The product for inhibiting the expression, activity or function of the LINC00839 gene comprises any one of the following components: B1. Sgrnas targeting LINC00839 gene; B2. shRNA targeting LINC00839 gene; B3. siRNA targeting LINC00839 gene; B4. miRNA targeting LINC00839 gene; B5. Antisense oligonucleotide ASO of targeted LINC00839 gene; B6. A blocker, antagonist or inhibitor targeting the LINC00839 gene, inhibiting its expression/activity/function; B7. a plasmid vector, lentiviral vector, adenoviral vector, adeno-associated vector or sgRNA ribonucleoprotein complex comprising the sgRNA described in B1; B8. a plasmid vector, lentiviral vector, adenoviral vector or adenovirus-associated vector comprising the shRNA described in B2; B9. A plasmid vector, lentiviral vector, adenoviral vector or adenovirus-associated vector comprising the siRNA described in B3; B10. A plasmid vector, lentiviral vector, adenoviral vector or adenovirus-associated vector comprising the miRNA described in B4.
  3. 3. The use according to claim 1, wherein the iron death inducing agent comprises sorafenib, erastin and RSL3.
  4. 4. A pharmaceutical composition for treating nasopharyngeal carcinoma, said pharmaceutical composition comprising an iron death inducer and a product that inhibits expression, activity or function of an ELK1 gene or a LINC00839 gene.
  5. 5. The pharmaceutical composition of claim 4, wherein the product that inhibits expression, activity or function of ELK1 gene comprises any one of: A1. Sgrnas targeting ELK1 genes; A2. shRNA targeting ELK1 gene; A3. siRNA targeting ELK1 gene; A4. miRNA targeting ELK1 gene; A5. Antisense oligonucleotide ASO of targeted ELK1 gene; A6. a blocker, antagonist or inhibitor targeting the ELK1 gene, inhibiting its expression, activity or function; A7. a plasmid vector, lentiviral vector, adenoviral vector, adeno-associated vector or sgRNA ribonucleoprotein complex comprising the sgRNA described in A1; A8. A plasmid vector, lentiviral vector, adenoviral vector or adenovirus-associated vector comprising the shRNA described in A2; A9. a plasmid vector, lentiviral vector, adenoviral vector or adenovirus-associated vector comprising the siRNA described in A3; A10. A plasmid vector, lentiviral vector, adenoviral vector or adenovirus-associated vector comprising the miRNA described in A4; The product for inhibiting the expression, activity or function of the LINC00839 gene comprises any one of the following components: B1. Sgrnas targeting LINC00839 gene; B2. shRNA targeting LINC00839 gene; B3. siRNA targeting LINC00839 gene; B4. miRNA targeting LINC00839 gene; B5. Antisense oligonucleotide ASO of targeted LINC00839 gene; B6. A blocker, antagonist or inhibitor targeting the LINC00839 gene, inhibiting its expression/activity/function; B7. a plasmid vector, lentiviral vector, adenoviral vector, adeno-associated vector or sgRNA ribonucleoprotein complex comprising the sgRNA described in B1; B8. a plasmid vector, lentiviral vector, adenoviral vector or adenovirus-associated vector comprising the shRNA described in B2; B9. A plasmid vector, lentiviral vector, adenoviral vector or adenovirus-associated vector comprising the siRNA described in B3; B10. A plasmid vector, lentiviral vector, adenoviral vector or adenovirus-associated vector comprising the miRNA described in B4.
  6. 6. The pharmaceutical composition of claim 4, wherein the iron death inducing agent comprises sorafenib, erastin, and RSL3.
  7. 7. The application of a product over-expressing ELK1 gene or LINC00839 gene in preparing a tumor cell model with iron death resistance.
  8. 8. The method for constructing the tumor cell model with the iron death resistance is characterized by comprising the step of transferring an ELK1 gene or a LINC00839 gene into a tumor cell to enable the ELK1 gene or the LINC00839 gene to be over-expressed in the tumor cell, and constructing the tumor cell model.
  9. 9. A tumor cell model constructed by the method of claim 8.
  10. 10. Use of the tumor cell model of claim 9 for screening a drug capable of improving the therapeutic effect of an iron death inducer of nasopharyngeal carcinoma.

Description

Application of ELK1 and LINC00839 genes in regulation and control of treatment effect of nasopharyngeal iron death inducer Technical Field The invention relates to the technical field of genetic engineering, in particular to application of ELK1 and LINC00839 genes in regulating and controlling treatment effect of a nasopharyngeal carcinoma iron death inducer. Background Nasopharyngeal carcinoma (NPC) is an invasive tumor. Although early nasopharyngeal carcinoma patients have a good prognosis due to the development of integrated treatment, most advanced patients are still at risk of high recurrence rate and distant metastasis. At present, recurrence and metastasis remain the main causes of treatment failure of nasopharyngeal carcinoma and death of patients. Thus, revealing specific mechanisms of nasopharyngeal carcinoma progression is of great importance for developing novel therapeutic strategies. Iron death is a novel cell death modality characterized by iron accumulation and lipid peroxidation, and is involved in a variety of disease processes including nasopharyngeal carcinoma. Iron death inducers are involved in the therapeutic response of a variety of human malignancies, including nasopharyngeal carcinoma. In addition, both chemotherapy and radiation therapy can exert therapeutic effects by triggering iron death in cancer cells. Iron death resistance is considered to be an important driver of chemotherapy resistance to nasopharyngeal carcinoma. Thus, induction of iron death has been considered as a new approach to delay the progression of nasopharyngeal carcinoma, and exploration of potential mechanisms of iron death resistance in nasopharyngeal carcinoma has helped to improve therapeutic effects. Sorafenib is a multi-target oral tyrosine kinase inhibitor that exerts an antitumor effect by inducing iron death. Sorafenib is used mainly as part of a combination treatment regimen in nasopharyngeal carcinoma, and when used in combination with conventional chemotherapeutic agents (cisplatin, 5-FU), can significantly improve objective remission rates and extend survival. However, clinical applications often face the challenge of tumor cells to develop resistance to iron death by sorafenib. Therefore, it is necessary to research the drug resistance mechanism of sorafenib induced iron death and the potential reversing strategy thereof in nasopharyngeal carcinoma, so as to provide theoretical basis and potential new therapeutic targets for overcoming iron death resistance in nasopharyngeal carcinoma treatment, and finally improve prognosis of patients with advanced and drug-resistant nasopharyngeal carcinoma. Disclosure of Invention The invention aims to provide application of ELK1 and LINC00839 genes in regulating and controlling treatment effect of nasopharyngeal iron death inducer, so as to solve the problems in the prior art. The invention discloses a key role of ELK1 gene and LINC00839 gene in regulating iron death sensitivity of nasopharyngeal carcinoma cells. Inhibiting the expression of ELK1 or LINC00839 can significantly increase the sensitivity of nasopharyngeal carcinoma cells to iron death inducers such as sorafenib, erastin, RSL3, etc., whereas over-expressing ELK1 or LINC00839 can significantly decrease the sensitivity of nasopharyngeal carcinoma cells to iron death. In order to achieve the above object, the present invention provides the following solutions: The invention provides application of a product for inhibiting the expression, activity or function of ELK1 gene or LINC00839 gene in preparing a medicament for improving the treatment effect of a nasopharyngeal carcinoma iron death inducer. Further, the product that inhibits the expression, activity or function of the ELK1 gene includes any one of the following: A1. Sgrnas targeting ELK1 genes; A2. shRNA targeting ELK1 gene; A3. siRNA targeting ELK1 gene; A4. miRNA targeting ELK1 gene; A5. Antisense oligonucleotide ASO of targeted ELK1 gene; A6. a blocker, antagonist or inhibitor targeting the ELK1 gene, inhibiting its expression, activity or function; A7. a plasmid vector, lentiviral vector, adenoviral vector, adeno-associated vector or sgRNA ribonucleoprotein complex comprising the sgRNA described in A1; A8. A plasmid vector, lentiviral vector, adenoviral vector or adenovirus-associated vector comprising the shRNA described in A2; A9. a plasmid vector, lentiviral vector, adenoviral vector or adenovirus-associated vector comprising the siRNA described in A3; A10. A plasmid vector, lentiviral vector, adenoviral vector or adenovirus-associated vector comprising the miRNA described in A4; The product for inhibiting the expression, activity or function of the LINC00839 gene comprises any one of the following components: B1. Sgrnas targeting LINC00839 gene; B2. shRNA targeting LINC00839 gene; B3. siRNA targeting LINC00839 gene; B4. miRNA targeting LINC00839 gene; B5. Antisense oligonucleotide ASO of targeted LINC00839 gene; B6. A blocker, antago