MAT2B inhibitor and application thereof in preparation of medicine for treating esophageal squamous carcinoma

Abstract

The invention relates to the technical field of MAT2B inhibitors and application thereof, in particular to an MAT2B inhibitor and application thereof in preparation of drugs for treating esophageal squamous carcinoma, the MAT2B inhibitor is siRNA or shRNA interfering with MAT2B expression, the siRNA comprises siRNA # 1 or / and siRNA # 2, and the shRNA comprises shRNA # 1 or / and shRNA # 2. According to the application, MAT2B is proposed as a potential oncogene for the first time, H3K79me2 methylation can be induced by promoting SAM generation so as to up-regulate E2F1 expression, proliferation of esophageal squamous carcinoma cells is further promoted, MAT2B inhibitor is used for interfering with MAT2B expression, proliferation of esophageal squamous carcinoma cells is further inhibited, and therefore the MAT2B is applied to preparation of the medicine for preventing or / and treating esophageal squamous carcinoma.

Description

Technical Field

[0001] This invention relates to the field of MAT2B inhibitors and their application technology, specifically a MAT2B inhibitor and its application in the preparation of drugs for treating esophageal squamous cell carcinoma. Background Technology

[0002] Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors worldwide. The incidence and mortality rates of ESCC in my country remain among the highest in the world. Current treatment for ESCC still relies on the traditional model of surgery combined with postoperative radiotherapy and chemotherapy, with a five-year survival rate remaining below 20%. Several recent studies have demonstrated that combining chemotherapy with PD-1 blockade can effectively improve the survival time of patients with advanced ESCC; however, the median improvement in survival time is only about 3 months, indicating significant individual variability in this treatment approach. Therefore, to achieve better clinical outcomes for esophageal cancer patients, it is urgent to find new ideas and targets for early diagnosis, treatment strategies, and prognostic assessment of esophageal cancer.

[0003] E2F1, a cell cycle-related transcription factor, is a member of the E2F family of cell cycle-related transcription factors. It is mainly involved in various cellular processes, including cell cycle progression, DNA repair, DNA replication, cell differentiation, proliferation, and apoptosis. E2F1 is highly expressed in various tumor tissues and cells throughout the body, acting as an oncogene. Upregulation of E2F1 expression is closely related to tumor occurrence, development, metastasis, and prognosis.

[0004] Methionine metabolism plays a crucial role in the development and progression of tumors, serving as a vital component of tumor metabolic reprogramming. Restricting methionine levels in the culture environment can inhibit the development and progression of prostate cancer, colorectal cancer, and melanoma. Methionine adenosyltransferase (MAT), a key enzyme in the reaction of methionine with ATP to generate SAM, exhibits altered gene expression in disease-related processes. The protein encoded by the MAT2B gene is a regulatory subunit of MAT. The MAT2B gene is highly expressed in human esophageal squamous cell carcinoma tissue; downregulation of the MAT2B gene leads to a decrease in intracellular SAM levels in tumor cells, resulting in significant inhibition of cell proliferation.

[0005] Chinese patent document CN114672551B discloses biomarkers MAT2A and MAT2B associated with benign prostatic hyperplasia (BPH), and also discloses the application of MAT2A and MAT2B as biomarkers in the preparation of products for diagnosing BPH. By downregulating the expression of MAT2A and MAT2B through the specific inhibitors PF-9366 and siRNA, the proliferation of human prostatic epithelial cell line WPMY-1 is inhibited, thereby achieving the effect of preventing and treating BPH, and its application in the preparation of drugs for the treatment of BPH.

[0006] Chinese patent document CN115844919A discloses a dual nucleic acid sequence for inhibiting melanoma growth and its application, as well as the application of a substance that reduces the expression levels of the ITK gene and MAT2B gene in the preparation of drugs for treating or preventing melanoma.

[0007] The above studies suggest that MAT2B can regulate the methionine metabolite SAM in tumor cells, promoting malignant tumor progression and causing tumor cells to develop resistance to clinical treatment. However, its specific mechanism of action in esophageal squamous cell carcinoma remains unclear. Although the diagnosis and treatment of esophageal cancer have made great strides in recent years, patients with esophageal squamous cell carcinoma still experience unsatisfactory responses to various treatments, including immunotherapy. Exploring the molecular mechanism by which MAT2B regulates tumor methionine metabolism in esophageal squamous cell carcinoma can provide a theoretical basis and new strategies and perspectives for individualized treatment of patients. Summary of the Invention

[0008] This invention provides a MAT2B inhibitor and its application in the preparation of drugs for treating esophageal squamous cell carcinoma, overcoming the shortcomings of the prior art and effectively solving the problem that existing esophageal squamous cell carcinoma patients do not respond well to various treatment methods, including immunotherapy.

[0009] One of the technical solutions of the present invention is achieved through the following measures: a MAT2B inhibitor, which is an siRNA or shRNA that interferes with MAT2B expression, wherein the siRNA includes siRNA#1 and / or siRNA#2, the shRNA includes shRNA#1 and / or shRNA#2, the sense strand of siRNA#1 is: CUGCCUCUCAACUUAAUGUTT, the antisense strand is ACAUUAAGUUGAGAGGCAGTT, the sense strand of siRNA#2 is: GCUCAGAUUAUGUAUUUGATT, the antisense strand is UCAAAUACAUAAUCUGAGCTT, the nucleotide sequence of shRNA#1 is: 5'-GCTGTGACTGTTATGTTTGAT-3', and the nucleotide sequence of shRNA#2 is: 5'-GCAGTTCATCACATCATTCAT-3'.

[0010] The following are further optimizations and / or improvements to one of the above-mentioned technical solutions: The above-mentioned inhibitory effect on the proliferation of esophageal squamous cell carcinoma cells.

[0011] The above-mentioned inhibition of H3K79me2 methylation level and E2F1 expression in esophageal squamous cell carcinoma cells.

[0012] The above can be used alone or in combination with other drugs.

[0013] When used in combination with other drugs, the other drugs are traditional cytotoxic drugs, molecularly targeted drugs, antitumor drugs, or other types of ingredients with antitumor activity.

[0014] The second technical solution of the present invention is achieved through the following measures: the application of a MAT2B inhibitor in the preparation of drugs for the prevention and / or treatment of esophageal squamous cell carcinoma, wherein the MAT2B inhibitor is an siRNA or shRNA that interferes with MAT2B expression, wherein the siRNA includes siRNA#1 and / or siRNA#2, and the shRNA includes shRNA#1 and / or shRNA#2, the sense strand of siRNA#1 is: CUGCCUCUCAACUUAAUGUTT, the antisense strand is ACAUUAAGUUGAGAGGCAGTT, the sense strand of siRNA#2 is: GCUCAGAUUAUGUAUUUGATT, the antisense strand is UCAAAUACAUAAUCUGAGCTT, the nucleotide sequence of shRNA#1 is: 5'-GCTGTGACTGTTATGTTTGAT-3', and the nucleotide sequence of shRNA#2 is: 5'-GCAGTTCATCACATCATTCAT-3'.

[0015] The following are further optimizations and / or improvements to the second technical solution of the above invention: The aforementioned MAT2B inhibitors inhibit the proliferation of esophageal squamous cell carcinoma cells.

[0016] The aforementioned MAT2B inhibitors suppress H3K79me2 methylation levels and E2F1 expression in esophageal squamous cell carcinoma cells.

[0017] The MAT2B inhibitors described above can be used alone or in combination with other drugs.

[0018] When the MAT2B inhibitors described above are used in combination with other drugs, the other drugs are traditional cytotoxic drugs, molecularly targeted drugs, antitumor drugs, or other types of ingredients with antitumor activity.

[0019] This invention proposes for the first time that MAT2B is a potential oncogene that can upregulate E2F1 expression by promoting SAM production and inducing H3K79me2 methylation, thereby promoting the proliferation of esophageal squamous cell carcinoma cells. By using MAT2B inhibitors to interfere with MAT2B expression, the proliferation of esophageal squamous cell carcinoma cells can be further inhibited, thus making it applicable to the preparation of drugs for the prevention and / or treatment of esophageal squamous cell carcinoma. Attached Figure Description

[0020] Appendix Figure 1A This is a graph showing the relative expression levels of MAT2B in esophageal squamous cell carcinoma and normal esophageal tissue samples in this invention.

[0021] Appendix Figure 1B This is a Kaplan-Meier survival curve diagram in this invention.

[0022] Appendix Figure 1C This is an immunohistochemical staining image of MAT2B in esophageal squamous cell carcinoma tissue and adjacent tissue in this invention.

[0023] Appendix Figure 2A This is a GSEA enrichment analysis diagram of the TCGA-esophageal squamous cell carcinoma dataset in this invention.

[0024] Appendix Figure 2B This is a graph showing the proliferation capacity of KYSE-150 after MAT2B interference detected by the CCK-8 method in this invention.

[0025] Appendix Figure 2C This is a graph showing the proliferation capacity of KYSE-150 after interference with MAT2B, as detected by the EdU experiment in this invention.

[0026] Appendix Figure 2D This is a diagram showing the cloning ability of KYSE-150 after interference with MAT2B, as detected by the plate clone formation experiment in this invention.

[0027] Appendix Figure 3A This is a graph showing the SAM content of KYSE-150 after MAT2B interference detected by ELISA in this invention.

[0028] Appendix Figure 3B This is a diagram showing the expression of H3K79me2 protein in KYSE-150 after MAT2B interference, as detected by immunoblotting in this invention.

[0029] Appendix Figure 3C This is a GSEA enrichment analysis diagram when SAM is downregulated in KYSE-150 in this invention.

[0030] Appendix Figure 3D This is a graph showing the tracks when SAM is down-adjusted in KYSE-150 in this invention.

[0031] Appendix Figure 3EThis is a diagram showing the chromatin immunoprecipitation results when SAM is downregulated in KYSE-150 in this invention.

[0032] Appendix Figure 3F This is a diagram showing the expression of E2F1 protein in KYSE-150 after MAT2B interference, as detected by immunoblotting in this invention.

[0033] Appendix Figure 4A This is a diagram showing the expression of H3K79me2 and E2F1 proteins in KYSE-150 after immunoblotting and treatment with exogenous SAM, which were detected by MAT2B interference and the addition of exogenous SAM in this invention.

[0034] Appendix Figure 4B This is a graph showing the proliferation capacity of KYSE-150 after CCK-8 assay with interference MAT2B and addition of exogenous SAM, as used in this invention.

[0035] Appendix Figure 4C This is a graph showing the proliferation capacity of KYSE-150 after EdU method detection of interfering MAT2B and treatment with exogenous SAM in this invention. Detailed Implementation

[0036] This invention is not limited to the following embodiments; specific implementation methods can be determined based on the technical solution of this invention and actual circumstances. Unless otherwise specified, all chemical reagents and chemical products mentioned in this invention are well-known and commonly used chemical reagents and chemical products in the prior art.

[0037] The present invention will be further described below with reference to embodiments: Example 1: The MAT2B inhibitor is a siRNA or shRNA that interferes with MAT2B expression. The siRNA includes siRNA#1 and / or siRNA#2, and the shRNA includes shRNA#1 and / or shRNA#2. The sense strand of siRNA#1 is: CUGCCUCUCAACUUAAUGUTT, and the antisense strand is ACAUUAAGUUGAGAGGCAGTT. The sense strand of siRNA#2 is: GCUCAGAUUAUGUAUUUGATT, and the antisense strand is UCAAAUACAUAAUCUGAGCTT. The nucleotide sequence of shRNA#1 is: 5'-GCTGTGACTGTTATGTTTGAT-3', and the nucleotide sequence of shRNA#2 is: 5'-GCAGTTCATCACATCATTCAT-3'.

[0038] Example 2: As an optimization of the above example, the proliferation of esophageal squamous cell carcinoma cells was inhibited.

[0039] Example 3: As an optimization of the above examples, the methylation level of H3K79me2 and the expression of E2F1 in esophageal squamous cell carcinoma cells were inhibited.

[0040] Example 4: As an optimization of the above examples, it can be used alone or in combination with other drugs.

[0041] Example 5: As an optimization of the above examples, when used in combination with other drugs, the other drugs are traditional cytotoxic drugs, molecularly targeted drugs, antitumor drugs, or other types of ingredients with antitumor activity.

[0042] Example 6: Application of the MAT2B inhibitor in the preparation of drugs for the prevention and / or treatment of esophageal squamous cell carcinoma. The MAT2B inhibitor is a siRNA or shRNA that interferes with MAT2B expression. The siRNA includes siRNA#1 and / or siRNA#2, and the shRNA includes shRNA#1 and / or shRNA#2. The sense strand sequence of siRNA#1 is shown in SEQ ID NO.1, specifically: CUGCCUCUCAACUUAAUGUTT, and the antisense strand sequence is shown in SEQ ID NO.2, specifically: ACAUUAAGUUGAGAGGCAGTT. The sense strand sequence of siRNA#2 is shown in SEQ ID NO.3, specifically: GCUCAGAUUAUGUAUUUGATT, and the antisense strand sequence is shown in SEQ ID NO.4, specifically: UCAAAUACAUAAUCUGAGCTT. The nucleotide sequence of shRNA#1 is shown in SEQ ID NO.5, specifically: 5'-GCTGTGACTGTTATGTTTGAT-3'. The nucleotide sequence of shRNA#2 is shown in SEQ ID NO. As shown in NO.6, specifically: 5'-GCAGTTCATCACATCATTCAT-3'.

[0043] Example 7: As an optimization of the above examples, the MAT2B inhibitor inhibits the proliferation of esophageal squamous cell carcinoma cells.

[0044] Example 8: As an optimization of the above example, the MAT2B inhibitor inhibits the H3K79me2 methylation level and E2F1 expression in esophageal squamous cell carcinoma cells.

[0045] Example 9: As an optimization of the above examples, the MAT2B inhibitor may be used alone or in combination with other drugs.

[0046] Example 10: As an optimization of the above example, when the MAT2B inhibitor is used in combination with other drugs, the other drugs are traditional cytotoxic drugs, molecularly targeted drugs, antitumor drugs, or other types of components with antitumor activity.

[0047] This invention utilizes the UACLAN online database to analyze the expression level of the MAT2B gene, classifies samples from the TCGA-ESCA database according to pathological type, and statistically analyzes the mRNA expression level of MAT2B in each sample (e.g., Figure 1A (As shown). Figure 1A It can be seen that in the TCGA-esophageal squamous cell carcinoma dataset, the expression level of MAT2B in human esophageal squamous cell carcinoma tissues is higher than that in adjacent normal tissues. Based on the mRNA expression level of MAT2B, samples in the GSE53622 database were classified, and survival curves were plotted using clinical data (e.g., Figure 1B (As shown). Figure 1B As can be seen, the Kaplan-Meier survival curve shows that patients with esophageal squamous cell carcinoma who have high MAT2B expression have shorter overall survival. Next, immunohistochemical staining was performed on esophageal squamous cell carcinoma samples that underwent surgical resection without radiotherapy or chemotherapy. Immunohistochemical experiments were conducted to compare the expression levels of MAT2B in normal esophageal tissue and esophageal squamous cell carcinoma tumor tissue (e.g., ...). Figure 1C (As shown). Figure 1C It can be seen that the staining area and intensity of MAT2B protein in esophageal squamous cell carcinoma samples are higher than those in adjacent tissues.

[0048] To explore the potential role of MAT2B in esophageal squamous cell carcinoma, bioinformatics analysis was performed on the TCGA-esophageal squamous cell carcinoma dataset (e.g., Figure 2A (as shown) Figure 2A It can be seen that high expression of MAT2B can upregulate the E2F pathway, which is related to cell proliferation. Figure 2AThe samples and sequencing results used for enrichment analysis were obtained from the TCGA-ESCC public database. Samples in this database were sorted and classified according to MAT2B mRNA expression levels: samples with the median expression were classified as the MAT2B high-expression group (marked in red on the left side of the figure as "MAT2B_HIGH"), and those with the median expression were classified as the MAT2B low-expression group (marked in blue on the right side of the figure as "MAT2B_LOW"). Enrichment analysis of the sequencing results in the HALLMARK and KEGG gene sets was performed using the GSEA desktop software. (The interpretation criteria were: Nominalp value < 0.5 and FDR value < 0.25 were considered statistically significant; NES > 1 indicated that the treatment on the left side could upregulate the corresponding cellular pathway or cellular function.) GSEA enrichment results showed that high MAT2B expression significantly upregulated the cell proliferation-related gene set E2F_TARGETS. These results suggest that limiting methionine intake can promote the proliferation of esophageal squamous cell carcinoma cells with MAT2B.

[0049] Based on the results of the above bioinformatics analysis, the cell line KYSE-150, which has high endogenous MAT2B protein expression, was selected for subsequent experiments related to MAT2B interference.

[0050] First, the proliferation capacity of the esophageal squamous cell carcinoma cell line KYSE-150 was detected using the CCK-8 assay (e.g., Figure 2B As shown), the proliferation capacity of the esophageal squamous cell carcinoma cell line KYSE-150 was detected using the EdU assay (e.g., Figure 2C (As shown). Figures 2B-2C It can be seen that the proliferation ability of esophageal squamous cell carcinoma cells in the siMAT2B group was reduced compared with that in the control group. The proliferation ability of the esophageal squamous cell carcinoma cell line KYSE-150 was detected using a plate colony formation assay (e.g., Figure 2D (as shown) Figure 2D It can be seen that the number of colonies formed by esophageal squamous cell carcinoma cells was significantly reduced after MAT2B interference.

[0051] in, Figure 2B In China, OD 450 Value: The absorbance value measured at 450 nm. Based on the experimental principle of CCK-8, this value can be considered positively correlated with cell proliferation capacity. The results showed that the proliferation capacity of KYSE-150 cells was significantly reduced after treatment with MAT2BsiRNA.

[0052] Figure 2C Based on the experimental principle of EdU, it can be assumed that, with the same number of cells, the number of EdU-labeled cells is positively correlated with cell proliferation capacity. The results showed that treatment with MAT2BsiRNA significantly reduced the proliferation capacity of KYSE-150 cells.

[0053] Figure 2D Based on the experimental principle of plate colony formation assay, it can be considered that the number of cell colonies is positively correlated with cell proliferation capacity. Cell colonies appear as purple dots in the above image. The results show that the proliferation capacity of KYSE-150 cells significantly decreased after treatment with MAT2BsiRNA.

[0054] To further investigate whether MAT2B can affect the malignant progression of esophageal squamous cell carcinoma by influencing SAM production in these cells, we used ELISA to detect SAM levels in the KYSE-150 esophageal squamous cell carcinoma cell line (e.g., SAM production). Figure 3A As shown, Figure 3A It can be seen that interfering with MTA2B can significantly downregulate the SAM level in ESCC cells. Western blot was used to detect the protein expression of H3K79me2 in the esophageal squamous cell carcinoma cell line KYSE-150 (e.g., Figure 3B (as shown) Figure 3B It can be seen that, compared with the control group, interfering with MAT2B expression in KYSE-150 can reduce the level of H3K79me2 protein.

[0055] On the other hand, this invention reduces the SAM content (e.g., methionine restriction) in KYSE-150 cells by treating them with methionine restriction (MR). Figure 3C (as shown) Figure 3C It can be seen that gene set enrichment analysis revealed that downregulation of SAM significantly downregulated the E2F pathway. Among these, Figure 3C In this study, samples used for transcriptomics sequencing were categorized into a methionine-restricted group (MR) and a control group (Ctrl). The sequencing results were enriched in the Hallmark and Kegg gene sets using GSEA desktop software. GSEA enrichment results showed that methionine restriction significantly downregulated the cell proliferation-related gene set E2F_TARGETS. These results suggest that restricting methionine intake and downregulating SAM can significantly inhibit the proliferation of esophageal squamous cell carcinoma cells.

[0056] Utilization for chromatin open accessibility sequencing (e.g.) Figure 3D (as shown) Figure 3D It can be seen that downregulation of SAM decreases the accessibility of E2F1 chromatin. Specifically, Figure 3D In the study, the samples used for chromatin accessibility sequencing were classified into the methionine-restricted group (MR) and the control group (Ctrl). The sequencing results showed that downregulation of SAM could lead to a decrease in chromatin accessibility in the E2F1 promoter region (shown as the MR group with a lower peak value corresponding to the shaded area in the figure).

[0057] The binding of H3K79me2 and E2F1 in the esophageal squamous cell carcinoma cell line KYSE-150 was detected using ChIP-qPCR. Figure 3E (As shown). Figure 3E It can be seen that the enrichment level of H3K79me2 in the E2F1 promoter subregion decreases when SAM is reduced. Among these, Figure 3E In the experiment, the samples used were classified into a methionine-restricted group (MR) and a control group (Ctrl). The results showed that after SAM was downregulated, the binding of H3K79me2 to E2F1 was significantly reduced.

[0058] Western blot analysis was used to detect the protein expression of E2F1 in the esophageal squamous cell carcinoma cell line KYSE-150 (e.g., Figure 3F (As shown). Figure 3F It can be seen that, compared with the control group, the E2F1 protein in KYSE-150 cells was significantly reduced after treatment with MAT2BshRNA.

[0059] To further clarify the mechanism by which MAT2B promotes SAM production and thus upregulates E2F1 expression in esophageal squamous cell carcinoma, this invention selected shMAT2B and supplemented exogenous SAM for rescue experiments. Western blot was used to detect the protein expression of H3K79me2, E2F1, and cell cycle markers CDC2 and CDK2 in the esophageal squamous cell carcinoma cell line KYSE-150 (e.g., Figure 4A (as shown) Figure 4A It can be seen that, compared with the control group, interfering with MAT2B expression in KYSE-150 cells led to a decrease in H3K79me2 and E2F1 protein levels. However, adding exogenous SAM to cells with MAT2B interference resulted in an increase in H3K79me2 and E2F1 protein levels compared to the interference group. This indicates that adding exogenous SAM can reverse the downregulation of H3K79me2 and E2F1 protein levels caused by MAT2B interference. Figure 4A In China, OD 450 Value: The absorbance value measured at 450 nm. Based on the experimental principle of CCK-8, this value can be considered positively correlated with cell proliferation capacity. The results showed that MAT2BshRNA could inhibit the proliferation of KYSE-150 cells, and the addition of SAM could reverse the inhibition of KYSE-150 cell proliferation by MAT2BshRNA.

[0060] The proliferative capacity of the esophageal squamous cell carcinoma cell line KYSE-150 was detected using the CCK-8 assay (e.g., Figure 4B As shown), the proliferation capacity of the esophageal squamous cell carcinoma cell line KYSE-150 was detected using the EdU assay (e.g., Figure 4C (As shown).

[0061] Figure 4B and 4C It can be seen that, compared with the control group, the cell proliferation capacity of the MAT2B-interference group was significantly reduced. However, the addition of exogenous SAM to the MAT2B-interference cells could reverse the inhibition of cell proliferation caused by MAT2B interference. Figure 4B In China, OD 450 Value: The absorbance value measured at 450 nm. Based on the experimental principle of CCK-8, this value can be considered positively correlated with cell proliferation capacity. The results showed that MAT2BshRNA could inhibit the proliferation of KYSE-150 cells, and the addition of SAM could reverse the inhibition of KYSE-150 cell proliferation by MAT2BshRNA. Figure 4C Based on the experimental principle of EdU, it can be assumed that, under the same cell number, the number of EdU-labeled cells is positively correlated with cell proliferation capacity. The results showed that MAT2B shRNA inhibited the proliferation of KYSE-150 cells, and the addition of SAM reversed the inhibition of KYSE-150 cell proliferation by MAT2B shRNA.

[0062] In summary, this invention proposes for the first time that MAT2B is a potential oncogene that can upregulate E2F1 expression by promoting SAM production and inducing H3K79me2 methylation, thereby promoting the proliferation of esophageal squamous cell carcinoma cells. By using MAT2B inhibitors to interfere with MAT2B expression, the proliferation of esophageal squamous cell carcinoma cells can be further inhibited, thus making it applicable to the preparation of drugs for the prevention and / or treatment of esophageal squamous cell carcinoma.

[0063] The above technical features constitute the embodiments of the present invention, which have strong adaptability and implementation effect. Unnecessary technical features can be added or removed according to actual needs to meet the needs of different situations.

Claims

1. A MAT2B inhibitor, characterized in that... The siRNA or shRNA used to interfere with MAT2B expression includes siRNA#1 and / or siRNA#2, and shRNA includes shRNA#1 and / or shRNA#2. The sense strand of siRNA#1 is: CUGCCUCUCAACUUAAUGUTT, and the antisense strand is ACAUUAAGUUGAGAGGCAGTT. The sense strand of siRNA#2 is: GCUCAGAUUAUGUAUUUGATT, and the antisense strand is UCAAAUACAUAAUCUGAGCTT. The nucleotide sequence of shRNA#1 is: 5'-GCTGTGACTGTTATGTTTGAT-3', and the nucleotide sequence of shRNA#2 is: 5'-GCAGTTCATCACATCATTCAT-3'.

2. The MAT2B inhibitor according to claim 1, characterized in that... It inhibits the proliferation of esophageal squamous cell carcinoma cells.

3. The MAT2B inhibitor according to claim 1 or 2, characterized in that... Inhibit H3K79me2 methylation level and E2F1 expression in esophageal squamous cell carcinoma cells.

4. The MAT2B inhibitor according to any one of claims 1 to 3, characterized in that... Use alone or in combination with other medications.

5. The MAT2B inhibitor according to claim 4, characterized in that... When used in combination with other drugs, the other drugs are traditional cytotoxic drugs, molecularly targeted drugs, antitumor drugs, or other types of ingredients with antitumor activity.

6. The use of a MAT2B inhibitor in the preparation of drugs for the prevention and / or treatment of esophageal squamous cell carcinoma, characterized in that... The MAT2B inhibitor is a siRNA or shRNA that interferes with MAT2B expression. The siRNA includes siRNA#1 and / or siRNA#2, and the shRNA includes shRNA#1 and / or shRNA#2. The sense strand of siRNA#1 is: CUGCCUCUCAACUUAAUGUTT, and the antisense strand is ACAUUAAGUUGAGAGGCAGTT. The sense strand of siRNA#2 is: GCUCAGAUUAUGUAUUUGATT, and the antisense strand is UCAAAUACAUAAUCUGAGCTT. The nucleotide sequence of shRNA#1 is: 5'-GCTGTGACTGTTATGTTTGAT-3', and the nucleotide sequence of shRNA#2 is: 5'-GCAGTTCATCACATCATTCAT-3'.

7. The use of the MAT2B inhibitor according to claim 6 in the preparation of drugs for the prevention and / or treatment of esophageal squamous cell carcinoma, characterized in that... The MAT2B inhibitor inhibits the proliferation of esophageal squamous cell carcinoma cells.

8. The use of the MAT2B inhibitor according to claim 6 or 7 in the preparation of drugs for the prevention and / or treatment of esophageal squamous cell carcinoma, characterized in that... The MAT2B inhibitor inhibits H3K79me2 methylation levels and E2F1 expression in esophageal squamous cell carcinoma cells.

9. The use of the MAT2B inhibitor according to claim 6, 7, or 8 in the preparation of drugs for the prevention and / or treatment of esophageal squamous cell carcinoma, characterized in that... The MAT2B inhibitor can be used alone or in combination with other drugs.

10. The use of the MAT2B inhibitor according to claim 9 in the preparation of drugs for the prevention and / or treatment of esophageal squamous cell carcinoma, characterized in that... When the MAT2B inhibitor is used in combination with other drugs, the other drugs are traditional cytotoxic drugs, molecularly targeted drugs, antitumor drugs, or other types of ingredients with antitumor activity.

Images