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CN-121987658-A - MiRNA miR-148b-3p for targeted regulation of action of SLC7A11 in iron death and action mechanism and application thereof

CN121987658ACN 121987658 ACN121987658 ACN 121987658ACN-121987658-A

Abstract

The invention provides miRNA miR-148b-3p for targeted regulation and control of the action of SLC7A11 in iron death, and an action mechanism and application thereof, and discovers and proves that miR-148b-3p can promote the iron death process of breast cancer cells and inhibit proliferation and migration of breast cancer cells through targeted regulation and control of SLC7A11 for the first time. Related action mechanisms are revealed through researches such as ceRNA network construction, and potential targets and strategies are provided for breast cancer treatment. Meanwhile, the compound has a regulating and controlling effect in other cancers but has weaker effect than that of breast cancer, the specific regulating and controlling effect on the breast cancer is highlighted, and a solid theoretical basis is laid for the accurate treatment of the breast cancer, so that the treatment and research of the breast cancer are more effectively carried out. Meanwhile, the regulation and control of miR-148b-3p on iron death are explored through various analyses, so that the regulation and control of iron death related genes can be regulated, and further cell survival and death are regulated and controlled. The method provides a new view for breast cancer treatment, provides a basis for researching biological behaviors of tumor cells, and has important application prospect.

Inventors

  • ZHANG LEI
  • MA GUANNAN
  • NIU KAIFENG
  • QIN LAN

Assignees

  • 杭州迪安医学检验中心有限公司

Dates

Publication Date
20260508
Application Date
20241105

Claims (10)

  1. 1. The application of miRNA in preparing a preparation for regulating iron death in tumor cells is characterized in that the miRNA is miR-148b-3p, and the nucleotide sequence of the miR-148b-3p is shown as SEQ ID NO.1 and SEQ ID NO. 2.
  2. 2. The use of claim 1, wherein the gene associated with iron death in the tumor cell is the SLC7A11 gene, and wherein the expression of the SLC7A11 gene is regulated by regulating the expression level of miR-148b-3p, thereby regulating iron death in the tumor cell.
  3. 3. The use of claim 2, wherein iron death in tumor cells is promoted or inhibited by up-regulating or down-regulating miR-148b-3p expression and inhibiting or promoting expression of the SLC7a11 gene.
  4. 4. The use of claim 3, wherein the expression of the SLC7A11 gene is inhibited by adding a miR-148b-3p analog, iron death in the tumor cell is promoted, and wherein the expression of the SLC7A11 gene is increased by adding a miR-148b-3p inhibitor, and iron death in the tumor cell is inhibited.
  5. 5. The use of claim 4, wherein the miR-148b-3p inhibitor has a nucleotide sequence set forth in seq id No. 3.
  6. 6. The use of claim 5, wherein the miR-148b-3p analog or miR-148b-3p inhibitor is added to the tumor cell via a transfection reagent.
  7. 7. The use of claim 6, wherein the tumor cells comprise any one or a combination of breast cancer cells, colon cancer cells, or liver cancer cells.
  8. 8. The use of claim 7, wherein the tumor cells comprise breast cancer cells.
  9. The application of the miR-148b-3p inhibitor in preparing a preparation for regulating iron death in tumor cells is characterized in that the nucleotide sequence of the miR-148b-3p inhibitor is shown as SEQ ID NO. 3.
  10. 10. The use of claim 9, wherein increasing expression of the SLC7A11 gene by adding a miR-148b-3p inhibitor inhibits iron death in tumor cells, including breast cancer cells, colon cancer cells, or a combination of any one or more of liver cancer cells.

Description

MiRNA miR-148b-3p for targeted regulation of action of SLC7A11 in iron death and action mechanism and application thereof Technical Field The invention relates to the technical field of biology, in particular to miRNA miR-148b-3p for targeted regulation of action of SLC7A11 in iron death, and an action mechanism and application thereof. Background Cancer is one of the diseases that severely threatens human health worldwide, and its occurrence and development involves a variety of complex molecular mechanisms. In recent years, it has been found that solute carrier family 7 member 11 (SLC 7a 11) plays an important role in cancer. SLC7a11 is a multipass transmembrane protein that mediates extracellular cystine uptake and exchange glutamate, playing a vital role in cell growth, proliferation and metabolism. As a key cellular mechanism against iron death, the SLC7a11-GSH system affects intracellular cystine and glutathione levels by regulating cystine metabolic pathways, thereby affecting cell death. Currently, more and more studies indicate that SLC7a11 is overexpressed in a variety of tumors, the expression levels of which are closely related to tumor cell proliferation, invasion, metastasis and tumor microenvironment. For example, in lung cancer, has-mir-373 and Has-mir-372 can up-regulate SLC7A11 expression by competitive binding, regulate immune infiltration in lung adenocarcinoma, in melanoma SLC7A11 increases intracellular GSH levels, confers resistance to BRAF inhibitors, and in bladder cancer, inhibition of SLC7A11 expression can reverse resistance of resistant cells to cisplatin. However, there is little systematic study on SLC7a11 in pan-carcinoma, and the underlying molecular mechanisms of its level changes during cancer formation are not yet fully understood. In breast cancer, the expression of SLC7A11 is positively correlated with tumor immune cell infiltration, and high expression is obviously correlated with poor prognosis, which suggests that the SLC7A11 can be used as a biomarker for the poor prognosis of breast cancer patients. However, it is not clear how cancer, particularly breast cancer, can be inhibited by SLC7A 11. Microribonucleic acid (miRNA) is an endogenous non-coding single-stranded RNA molecule, and can be combined with a 3' -untranslated region of a target gene to negatively regulate the expression and cell functions of the target gene. Studies have shown that miR-148a-3p promotes malignant behavior of breast cancer cells by downregulating DUSP1, but miRNA or mechanism for targeted regulation of SLC7A11 gene to inhibit breast cancer is not clear. Iron death, a new form of cell death that has received widespread attention in recent years, may play an important role in the development and progression of tumors. However, the specific mechanism of action and the role of the relevant regulatory factors in cancer is not completely understood. Therefore, in order to deeply understand the action mechanism of SLC7A11 in cancers, an effective method for inhibiting cancers, especially breast cancers, is sought, and an action mechanism of SLC7A11 for inhibiting cancers through regulating iron death and a novel miRNA capable of targeting and regulating SLC7A11 are needed to be found, and the purposes of inhibiting breast cancers are achieved through regulating and controlling the in vivo miRNA expression quantity and then targeting and regulating SLC7A11 genes. Disclosure of Invention In order to solve the problems in the prior art, the invention provides miRNA miR-148b-3p for targeted regulation and control of the action of SLC7A11 in iron death and an action mechanism and application thereof, which firstly make clear that miR-148b-3p can influence the iron death process of breast cancer cells through targeted regulation and control of SLC7A11, and verify the change of related indexes (MDA level, GSH level and cell activity) after transfection of miR-148b-3p inhibitor through cell experiments, so as to obtain a conclusion that miR-148b-3p can regulate iron death related genes and further regulate and control the survival and death of breast cancer cells, and simultaneously firstly disclose the regulation and control action mechanism of miR-148b-3p and SLC7A11 in the iron death of breast cancer cells, thereby providing new targets and ideas for breast cancer treatment and laying a theoretical basis for developing a breast cancer treatment strategy based on iron death regulation and control. In order to achieve the above purpose, the invention is realized by adopting the following scheme: In one aspect, the invention provides an application of miRNA (micro ribonucleic acid) in preparing a preparation for regulating proliferation activity or migration capacity of tumor cells, wherein the miRNA is miR-148b-3p, and the nucleotide sequence of miR-148b-3p is shown as SEQ ID NO.1 and SEQ ID NO. 2. In order to understand the action mechanism of SLC7A11 in cancer deeply, an effective method for inhibit