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CN-121971620-A - Use of long-chain non-coding RNA MILIP in colorectal cancer treatment

CN121971620ACN 121971620 ACN121971620 ACN 121971620ACN-121971620-A

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to application of long-chain non-coding RNA MILIP in colorectal cancer treatment. The invention discovers that LNCRNA MILIP gene is obviously higher than that of a paracancerous normal tissue and a normal colorectal cell line in colorectal tissues and colorectal cells, and can inhibit proliferation of colorectal cells and growth of tumors by inhibiting LNCRNA MILIP gene expression, so LNCRNA MILIP can be used as a treatment target of colorectal cancer, and LNCRNA MILIP inhibitor can prevent, relieve or/and treat colorectal cancer. The invention also discovers that the sensitivity of colorectal cancer cells to chemotherapeutic drugs can be improved by inhibiting LNCRNA MILIP gene expression, and DNA damage induced by the chemotherapeutic drugs is promoted, so that the LNCRNA MILIP inhibitor can be used for preparing colorectal cancer chemotherapeutic sensitizer, and the LNCRNA MILIP inhibitor and the chemotherapeutic drugs can be used together to obviously inhibit the growth of tumors.

Inventors

  • KOU JIAHUI
  • LI WENJIN
  • GUO SUTANG

Assignees

  • 山西医科大学

Dates

Publication Date
20260505
Application Date
20260211

Claims (10)

  1. 1. Use of LNCRNA MILIP inhibitors for any of the following: (A1) The application in preparing products for inhibiting tumor cell proliferation; (A2) The application of the composition in improving the sensitivity of tumor cells to chemotherapeutics or preparing products for improving the sensitivity of tumor cells to chemotherapeutics; (A3) Use in promoting DNA damage induced by a chemotherapeutic agent or in the manufacture of a product for promoting DNA damage induced by a chemotherapeutic agent; (A4) The application in preparing products for preventing, relieving or/and treating tumor; (A5) The application in preparing tumor chemosensitizer.
  2. 2. The use of claim 1, wherein the LNCRNA MILIP inhibitor comprises any one of: (B1) An agent that inhibits or reduces the expression or activity of LNCRNA MILIP genes; (B2) An agent that inhibits LNCRNA MILIP gene transcription into mRNA.
  3. 3. The use of claim 2 wherein said agent comprises at least one of SiRNA, shRNA, microRNA and wherein said SiRNA, shRNA, microRNA targets the expression of interfering LNCRNA MILIP genes.
  4. 4. The method of claim 3, wherein the SiRNA is SiRNA1 or SiRNA2, and the sense strand and antisense strand of SiRNA1 or SiRNA2 have the nucleotide sequences as follows: siRNA 1: the sense strand is 5'-GGAGUCAGGGCAAUUCCAATT-3' of the sequence, The antisense strand 5'-UUGGAAUUGCCCUGACUCCTT-3'; siRNA 2: the sense strand is 5'-GGUAACAUAGAGACCCUAUTT-3' of the sequence, The antisense strand 5'-AUAGGGUCUCUAUGUUACCTT-3'; the ShRNA is ShRNA1 or ShRNA2, and the nucleotide sequence of the forward oligonucleotide chain and the reverse oligonucleotide chain of ShRNA1 or ShRNA2 is as follows: ShRNA1: forward oligonucleotide strand: 5’-TCCCGGAGTCAGGGCAATTCCAATTCAAGAGAACGTGACACGTTCGGAGAATTTTTC-3’, Reverse oligonucleotide strand: 5’-TCGAGAAAAAGGAGTCAGGGCAAAAAAATCTCTTGAAACGTGACACGTTCGGAGAA-3’; ShRNA2: forward oligonucleotide strand: 5’-TCCCGGTAACATAGAGACCCTATTTCAAGAGAATAGGGTCTCTATGTTACCTTTTTC-3’, Reverse oligonucleotide strand: 5’-TCGAGAAAAAGGTAACATAGAGACCCTATTCTCTTGAAATAGGGTCTCTATGTTACC-3’。
  5. 5. the use according to any one of claims 1 to 4, wherein the tumour is colorectal cancer and the chemotherapeutic agent is a platinum-based chemotherapeutic agent.
  6. 6. A pharmaceutical composition comprising the LNCRNA MILIP inhibitor of any one of claims 1-5, wherein the pharmaceutical composition has at least one of the following uses: (C1) Inhibit tumor cell proliferation; (C2) Improving the sensitivity of tumor cells to chemotherapeutic drugs; (C3) Promoting DNA damage induced by chemotherapeutic agents; (C4) Enhancing sensitivity of chemotherapeutic drugs or enhancing tumor chemotherapeutic effect; (C5) Preventing, alleviating or/and treating tumors.
  7. 7. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition further comprises a chemotherapeutic agent.
  8. 8. The pharmaceutical composition according to claim 6 or 7, wherein the tumor is colorectal cancer and the chemotherapeutic is a platinum-based chemotherapeutic.
  9. 9. The pharmaceutical composition of claim 8, wherein the medicament further comprises a pharmaceutically acceptable adjuvant.
  10. 10. The LNCRNA MILIP is applied to screening candidate medicines for preventing, relieving or/and treating colorectal cancer, wherein the screening method is to screen medicines or reagents to be screened by taking LNCRNA MILIP as a target, so that medicines or reagents capable of inhibiting LNCRNA MILIP gene expression or/and function are used as candidate medicines for preventing, relieving or/and treating colorectal cancer.

Description

Use of long-chain non-coding RNA MILIP in colorectal cancer treatment Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to application of long-chain non-coding RNA MILIP in colorectal cancer treatment. Background Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide, as well as the second most lethal malignancy. So far, CRC has become one of the most serious challenges faced by many national medical systems. While early stage CRC may be cured by surgical excision with or without adjuvant chemotherapy, patients with advanced CRC, particularly those with liver metastases, still face undesirable clinical outcomes and significantly reduced survival rates. This poor prognosis is mainly due to the development of therapeutic resistance in CRC cells. Thus, there is an urgent need to elucidate the underlying molecular mechanisms and to identify new therapeutic targets. Long non-coding RNAs (lncRNAs) have attracted considerable attention due to their critical role in cancer genesis, progression and therapeutic resistance. Recent studies have revealed that interactions between lncRNAs and oxidative stress are critical for maintaining redox homeostasis in tumor cells. For example, in colorectal cancer, LINC01615 promotes the Pentose Phosphate Pathway (PPP), increases NADPH, decreases ROS, and supports survival and chemotherapy resistance through hnRNPA 1-mediated G6PD mRNA splicing. In hepatocellular carcinoma, LINC01532 also enhances G6PD splicing by hnRNPK, reduces ROS and drives lenvatinib resistance. Knocking down any lncRNA can restore drug sensitivity, and highlights the PPP regulatory lncRNA axis as a potential therapeutic target. Furthermore, hypoxia-induced NLUCAT a reduces ROS in early lung adenocarcinoma by transcriptional upregulation of antioxidant genes including aldehyde dehydrogenase 3A1 (ALDH 3 A1), glutathione peroxidase 2 (GPX 2), thioredoxin (GLRX), and pyruvate dehydrogenase kinase 4 (PDK 4), thereby promoting tumor cell proliferation. These findings not only elucidate the diverse regulatory mechanisms of lncRNAs in tumor antioxidant defense, but also provide a theoretical basis for novel anticancer strategies against lncRNA-oxidative stress axes. LNCRNAMILIP whether human chromosome 17q25.3,lncRNA MILIP is involved in the oncogenic regulatory network of colorectal cancer is not clear at present. Disclosure of Invention In view of the problems and deficiencies of the prior art, it is an object of the present invention to provide the use of long-chain non-coding RNA MILIP in the treatment of colorectal cancer. In order to achieve the aim of the invention, the technical scheme adopted by the invention is as follows: The first aspect of the invention provides the use of LNCRNA MILIP inhibitors for any of the following: (A1) The application in preparing products for inhibiting tumor cell proliferation; (A2) The application of the composition in improving the sensitivity of tumor cells to chemotherapeutics or preparing products for improving the sensitivity of tumor cells to chemotherapeutics; (A3) Use in promoting DNA damage induced by a chemotherapeutic agent or in the manufacture of a product for promoting DNA damage induced by a chemotherapeutic agent; (A4) The application in preparing products for preventing, relieving or/and treating tumor; (A5) The application in preparing tumor chemosensitizer. According to the above use, preferably, the LNCRNA MILIP inhibitor comprises any one of the following: (B1) An agent that inhibits or reduces the expression or activity of LNCRNA MILIP genes; (B2) An agent that inhibits LNCRNA MILIP gene transcription into mRNA. According to the above application, preferably, the agent comprises at least one of SiRNA, shRNA, microRNA, and the SiRNA, shRNA, microRNA targeting interferes with the expression of the LNCRNA MILIP gene. According to the above application, preferably, the SiRNA is SiRNA1 or SiRNA2, and the sense strand and antisense strand nucleotide sequences of SiRNA1 and SiRNA2 are as follows: siRNA 1: sense strand 5'-GGAGUCAGGGCAAUUCCAATT-3' (SEQ ID NO: 1), Antisense strand 5'-UUGGAAUUGCCCUGACUCCTT-3' (SEQ ID NO: 2); siRNA 2: Sense strand 5'-GGUAACAUAGAGACCCUAUTT-3' (SEQ ID NO: 3), Antisense strand 5'-AUAGGGUCUCUAUGUUACCTT-3' (SEQ ID NO: 4); the ShRNA is ShRNA1 or ShRNA2, and the nucleotide sequence of the forward oligonucleotide chain and the reverse oligonucleotide chain of ShRNA1 or ShRNA2 is as follows: ShRNA1: forward oligonucleotide strand: 5'-TCCCGGAGTCAGGGCAATTCCAATTCAAGAGAACGTGACACGTTCGGAGAATTTTTC-3' (SEQ ID NO: 5), Reverse oligonucleotide strand: 5'-TCGAGAAAAAGGAGTCAGGGCAAAAAAATCTCTTGAAACGTGACACGTTCGGAGAA-3' (SEQ ID NO: 6); ShRNA2: forward oligonucleotide strand: 5'-TCCCGGTAACATAGAGACCCTATTTCAAGAGAATAGGGTCTCTATGTTACCTTTTTC-3' (SEQ ID NO: 7), Reverse oligonucleotide strand: 5'-TCGAGAAAAAGGTAACATAGAGACCCTATTCTCTTGAAATAGGGTCTCTATGTTACC-3' (SEQ ID NO: 8). According t