Application of ACSS3 97th site lysine residue acetylation modification in preparation of lung cancer clinical diagnosis reagent

Abstract

The invention discloses application of ACSS3 97th site lysine residue acetylation modification in preparation of a lung cancer clinical diagnosis reagent, and belongs to the technical field of biomedicine. According to the application of acetylation modification of the lysine residue at the 97th site of the ACSS3 in preparation of the lung cancer clinical diagnosis reagent, the acetylation modification level of the lysine residue at the 97th site of the ACSS3 in lung cancer tissues is remarkably higher than that of para-carcinoma tissues, and the acetylation modification of the lysine residue at the 97th site of the ACSS3 affects the biological function of the ACSS3. The compound has the effects of promoting and maintaining survival and growth of lung cancer cells, and the acetylation level change can be used as a marker and a target spot for occurrence and development of lung cancer.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biomedical technology, more particularly to the application of the lysine residue at position 97 (K97) acetylation modification of ACSS3 in the preparation of a lung cancer clinical diagnosis reagent. BACKGROUND

[0002] Acyl-CoA synthetase short-chain family member 3 (ACSS3) is one of the members of the ACSSs family, which includes ACSS1, ACSS2, and ACSS3. The family can catalyze the generation of acetyl-CoA from short-chain fatty acids (SCFAs), providing energy sources for tumor cell metabolism. SCFAs include acetate, propionate, and butyrate, which are mainly produced by intestinal flora fermentation of dietary fiber. After being absorbed, they can be converted into acetyl-CoA by the ACSSs family, promoting tumor growth. ACSS3 is mainly located in the mitochondrial matrix and is highly expressed in the liver and kidney. It has high affinity for propionic acid and can convert propionic acid into propionyl-CoA, which is involved in the tricarboxylic acid cycle and gluconeogenesis metabolic pathways.

[0003] Abnormal expression of ACSS3 may play an important role in the occurrence and development of diseases. Its deletion will lead to propionate metabolism disorder, causing accumulation of propionate in serum, inducing autophagy of adipocytes, and causing metabolic diseases such as obesity and type II diabetes. In addition, ACSS3 produces acetyl-CoA by decomposing SCFAs, providing energy sources for the growth of tumor cells. It may play an important role in tumor metabolic reprogramming.

[0004] Lung cancer has the highest incidence and mortality rate worldwide. Current treatment methods include surgical resection, chemotherapy, and radiotherapy, but the overall efficacy is limited, and the 5-year survival rate of patients is still low. Although targeted therapy (such as EGFR and ALK inhibitors) has achieved remarkable results in some patients, drug resistance has limited its long-term application. Therefore, exploring new therapeutic targets is still an urgent need for lung cancer treatment.

[0005] Acetylation is an important post-translational modification of proteins, which is involved in the regulation of gene expression, signal transduction and metabolic pathways. In lung cancer, abnormal acetylation modification is closely related to the proliferation, metastasis and drug resistance of tumor cells. Acetyl-CoA, as a key substrate for acetylation, its level may be regulated by some metabolic enzymes in the case of hypoxia or energy deficiency. ACSS3, as a metabolic-related enzyme, plays an important role in fatty acid metabolism and tumor energy supply, and may affect tumor progression by regulating acetyl-CoA level and protein acetylation modification. It is not clear whether there is an acetylation modification site in ACSS3, and the role of the modification site in the development of lung cancer, and whether it can provide new ideas for the diagnosis and targeted treatment of lung cancer.

[0006] Therefore, the application of acetylation modification of lysine residue at the 97th site of ACSS3 in the preparation of a lung cancer clinical diagnosis reagent is an urgent problem for those skilled in the art to solve. SUMMARY

[0007] Therefore, the application of acetylation modification of lysine residue at the 97th site of ACSS3 in the preparation of a lung cancer clinical diagnosis reagent is an urgent problem for those skilled in the art to solve.

[0008] ACSS3 has acetylation modification at the lysine residue at the 97th site (K97), which has the effect of promoting and maintaining the survival and growth of lung cancer cells, and the change of the acetylation level can be used as a marker and a therapeutic target for the development of lung cancer.

[0009] In order to achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows:

[0010] ACSS3 has acetylation modification, and ACSS3 has acetylation modification at the lysine residue at the 97th site, and the amino acid sequence of the ACSS3 is shown as SEQ ID NO. 1.

[0011] The application of acetylation modification of ACSS3 at the lysine residue at the 97th site as a marker and a therapeutic target for the development of lung cancer, and the amino acid sequence of the ACSS3 is shown as SEQ ID NO. 1.

[0012] The application of acetylation modification of ACSS3 at the lysine residue at the 97th site in the preparation of a drug for inhibiting the growth, proliferation and / or migration of lung cancer cells, and the amino acid sequence of the ACSS3 is shown as SEQ ID NO. 1.

[0013] The application of acetylation modification of ACSS3 at the lysine residue at the 97th site as a target in the preparation of an anti-lung cancer drug, and the amino acid sequence of the ACSS3 is shown as SEQ ID NO. 1.

[0014] The application of the acetylation modification of ACSS3 at the lysine residue at position 97 in the preparation of a lung cancer diagnosis reagent or kit, wherein the amino acid sequence of the ACSS3 is shown as SEQ ID NO. 1.

[0015] The application of the acetylation modification of ACSS3 at the lysine residue at position 97 in the preparation of a lung cancer diagnosis or research cell sample, wherein the amino acid sequence of the ACSS3 is shown as SEQ ID NO. 1.

[0016] The application of the acetylation modification of ACSS3 at the lysine residue at position 97 in the preparation of a lung cancer diagnosis or research cell sample, wherein the amino acid sequence of the ACSS3 is shown as SEQ ID NO. 1.

[0017] A product, wherein the active ingredient of the product comprises the acetylation modification of ACSS3 at the lysine residue at position 97, and the amino acid sequence of the ACSS3 is shown as SEQ ID NO. 1; and the product has at least one of the following functions (1)-(5):

[0018] (1) predicting the risk of occurrence and development of lung cancer; (2) the elevated level indicating the occurrence of lung cancer and poor prognosis; (3) promoting and maintaining the survival and growth of lung cancer cells; (4) serving as a target for treating lung cancer; and (5) serving as a drug target for treating lung cancer.

[0019] According to the technical solution, compared with the prior art, the application provides the application of the acetylation modification of ACSS3 at the lysine residue at position 97 in the preparation of a lung cancer clinical diagnosis reagent, the acetylation modification of ACSS3 at the lysine residue at position 97 (K97) significantly increases the growth of lung cancer cells, can predict the risk of occurrence and development of lung cancer, can serve as a target for treating lung cancer, and is further applied to the prevention and prognosis of other tumor cells, and a new method for clinical lung cancer molecular diagnosis is provided, and a new drug target for the treatment of lung cancer is provided. BRIEF DESCRIPTION OF DRAWINGS

[0020] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed in the embodiments or prior art description will be briefly introduced below. Obviously, the drawings in the following description are only embodiments of the present application, and those skilled in the art can obtain other drawings according to the provided drawings without creative labor.

[0021] Figure 1 The expression level of the acetylation of ACSS3 K97 in lung cancer is shown in the schematic diagram of the ACSS3 acetylation modification and application of the present application.

[0022] A: lung cancer cell level; B: lung cancer tissue level; ***: P<0.001;

[0023] Figure 2 Figure 2 is a schematic diagram of the ROC curve of the ACSS3 K97 site acetylation level of the ACSS3 acetylation modification and application in the diagnosis of lung cancer;

[0024] Figure 3 Figure 3 is a schematic diagram of the correlation between the ACSS3 K97 site acetylation level of the ACSS3 acetylation modification and application and the prognosis of lung cancer patients;

[0025] wherein Number at risk represents the number of people who have not experienced an endpoint event at the time node corresponding to Time; *: P<0.05;

[0026] Figure 4 Figure 4 is a schematic diagram of H460 cells expressing ACSS3 K97 site deacetylation modification and ACSS3 K97 site acetylation modification protein of the ACSS3 acetylation modification and application;

[0027] Figure 5 Figure 5 is a schematic diagram of the effect of the ACSS3 K97 site acetylation of the ACSS3 acetylation modification and application on the growth of lung cancer cells;

[0028] wherein A: MTT experiment; B: colony formation experiment; ****: P<0.0001; ***: P<0.001;

[0029] Figure 6 Figure 6 is a schematic diagram of the effect of the ACSS3 K97 site acetylation of the ACSS3 acetylation modification and application on the migration / invasion of lung cancer cells;

[0030] wherein A: migration experiment; B: invasion experiment; ****: P<0.0001; **: P<0.001;

[0031] Figure 7 Figure 7 is a schematic diagram of the effect of the ACSS3 K97 site acetylation modification of the ACSS3 acetylation modification and application on the tumorigenicity of lung cancer cells;

[0032] wherein A: tumor volume; B: tumor weight, *: P<0.05. DETAILED DESCRIPTION

[0033] With reference to the accompanying drawings, the technical solutions in the embodiments of the present application will be described clearly and completely. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by a person of ordinary skill in the art without creative effort are within the protection scope of the present application.

[0034] The materials and reagents used in the following implementation cases can be obtained from commercial channels, and the quantitative experiments in the following implementation cases are set up in triplicate, and the average value is taken.

[0035] Example 1

[0036] As shown in Figure 1 , Figure 2 , Figure 3 , the expression level of the acetylation modification of lysine at the 97th site of ACSS3 (K97) in lung cancer cells and tissues is detected, and the correlation between the acetylation modification of lysine at the 97th site of ACSS3 and lung cancer diagnosis and prognosis is analyzed.

[0037] Experimental samples:

[0038] Protein lysate of lung cancer cell line (H460) and normal human bronchial epithelial cells (BEAS-2B).

[0039] Lung cancer patient tissue specimens (n=94) and paracancer tissue specimens (n=77).

[0040] Experimental method:

[0041] Western Blot: The acetylation level of lysine at the 97th site of ACSS3 in lung cancer cell line (H460) and normal human bronchial epithelial cells (BEAS-2B) is detected by using ACSS3 K97 acetylation antibody.

[0042] In the results of Western Blot analysis, compared with normal human bronchial epithelial cells (BEAS-2B), the expression level of lysine acetylation at the 97th site of ACSS3 in lung cancer cell line (H460) is increased (P<0.001).

[0043] Immunohistochemistry: The acetylation level of ACSS3 K97 in cancer tissues and paracancer tissues of lung cancer patients is detected by using ACSS3 K97 acetylation antibody.

[0044] In the analysis results of immunohistochemistry, the interpretation method of the original experimental data is as follows:

[0045] The intensity and positive rate of cytoplasmic staining are analyzed; the cancer tissues and paracancer tissues (epithelium) are interpreted respectively.

[0046] Standardization scheme of original experimental data:

[0047] Antibody: ACSS3 K97 acetylation antibody (K97);

[0048] Staining intensity score: 0 points (negative), 1 point (1+), 2 points (2+), 3 points (3+);

[0049] Staining positive rate score: 0%-100%;

[0050] Total score: "Staining intensity score" multiplied by "staining positive rate", (0-300%); the analysis results are as follows:

[0051] 1) Analysis of the expression difference of acetylated ACSS3 K97 in cancer and paracancer tissues

[0052] Analysis of ACSS3 K97 acetylation level in lung cancer tissues and paracancer tissues is shown in Table 1.

[0053] Table 1

[0054]

[0055] In the analysis results of immunohistochemistry, it was found by Mann-Whitney test that the expression level of ACSS3 K97 acetylation in lung cancer tissues (Cancer) was significantly higher than that in paracancer tissues (Paracancer) (P<0.001).

[0056] 2) Analysis of the correlation between acetylated ACSS3 K97 and lung cancer diagnosis and prognosis

[0057] (1) ROC curve analysis: comparing the positive rate of ACSS3 97 site lysine acetylation in lung cancer and paracancer tissues, the results showed that the AUC of ACSS3 97 site lysine acetylation positive rate in distinguishing lung cancer and paracancer tissues was 0.931 (95% confidence interval: 0.888-0.974).

[0058] (2) Analysis of the correlation between ACSS3 97 site lysine acetylation level and lung cancer patient prognosis: the immunohistochemistry results combined with Kaplan-Meier survival analysis method and log-rank statistical test were used for single factor analysis of survival period, and the results showed that the high expression of ACSS3 protein was significantly correlated with poor prognosis of lung cancer patients (P<0.05).

[0059] The above results show that, compared with human normal lung bronchial epithelial cells and lung cancer adjacent tissues, the ACSS3 K97 acetylation level in lung cancer cells and lung cancer tissues is significantly increased. It is indicated that the change of the acetylation level of this site can be used as a marker for monitoring the occurrence and development of lung cancer, and the risk of occurrence and development of lung cancer can be predicted, and the increase of the level indicates poor prognosis of lung cancer.

[0060] Therefore, the present application provides a new method for the molecular diagnosis of lung cancer for clinical use, and provides a new drug target for the treatment of lung cancer.

[0061] Example 2

[0062] The amino acid sequence of ACSS3 (NP_078836.1 acyl-CoA synthetase short-chain family member 3, mitochondrial isoform 1 precursor [Homo sapiens]) is shown as SEQ ID NO. 1.

[0063] MKPSWLQCRKVTSAGGLGGPLPGSSPARGAGAALRALVVPGPRGGLGGRGCRALSSGSGSEYKTHFAASVTDPERFWGKAAEQISWYKPWTKTLEN KHSPSTRWFVEGMLNICYNAVDRHIENGKGDKIAIIYDSPVTNTKATFTYKEVLEQVSKLAGVLVKHGIKKGDTVVIYMPMIPQAMYTMLACARIGAIHSLIFGGFASKELSSRIDHVKPKVVVTASFGIEPGRRVEYVPLVEEALKIGQHKPDKILIYNRPNMEAVPLAPGRDLDWDEEMAKAQSHDCVPVLSEHPLYILYTSGTTGLPKGVIRPTGGYAVMLHWSMSSIYGLQPGEVWWAASDLGWVVGHSYICYGPLLHGNTTVLYEGKPVGTPDAGAYFRVLAEHGVAALFTAPTAIRAIRQQDPGAALGKQYSLTRFKTLFVAGERCDVETLEWSKNVFRVPVLDHWWQTETGSPITASCVGLGNSKTPPPGQAGKSVPGYNVMILDDNMQKLKARCLGNIVVKLPLPPGAFSGLWKNQEAFKHLYFEKFPGYYDTMDAGYMDEEGYLYVMSRVDDVINVAGHRISAGAIEESILSHGTVADCAVVGKEDPLKGHVPLALCVLRKDINATEEQVLEEIVKHVRQNIGPVAAFRNAVFVKQLPKTRSGKIPRSALSAIVNGKPYKITSTIEDPSIFGHVEEMLKQA; SEQ ID NO. 1.

[0064] The ACSS3 nucleotide sequence is derived from the transcript provided by Yijin Biotech Co., Ltd., NCBI RefSeq: NM_024560.4, as shown in SEQ ID NO. 2.

[0065] ATGAAACCGTCTTGGCTGCAGTGTCGTAAAGTCACCAGCGCCGGGGGGCTCGGAGGGCCCTTGCCTGGGTCCTCTCCGGCCCGGGGAGCCGGTGCGGCCCTCAGGGCTTTAGTGGTCCCGGGCCCGCGGGGCGGTCTCGGGGGCCGGGGATGCAGGGCACTGTCCTCCGGCAGTGGCAGCGAGTACAAGACCCACTTCGCAGCCTCGGTGACCGACCCCGAGAGGTTCTGGGGCAAAGCTGCCGAGCAGATCAGCTGGTACAAGCCCTGGACCAAAACGCTGGAGAAC AAA

[0066] In view of the fact that the ACSS3 acetylation modification has not been disclosed, the present embodiment provides a new way of ACSS3 acetylation modification, i.e. the acetylation of the lysine residue at the 97th site (K97) of ACSS3. The lysine at the 97th site of the wild-type ACSS3 (the amino acid sequence is shown in SEQ ID NO. 1) is mutated to glutamine (the nucleotide sequence is that the "AAA" at 289-291 bp in SEQ ID NO. 2 is replaced by "CAA"), which simulates the acetylation modification of the K97 site of ACSS3. The lysine at the 97th site of the wild-type ACSS3 is mutated to arginine (the nucleotide sequence is that the "AAA" at 289-291 bp in SEQ ID NO. 2 is replaced by "AGA"), which simulates the deacetylation modification of the K97 site of ACSS3, which is used to construct lung cancer ACSS3 K97 site mutant cells and detect the effects of ACSS3 397 lysine acetylation modification on the proliferation, migration / invasion and tumorigenicity of lung cancer cells.

[0067] 1) Construction of lung cancer ACSS3 K97 site mutant cells

[0068] Experimental cells: H460 cells with ACSS3 knocked out constructed in the early stage, see the literature: Huang Qianqian, Jia Yufang, Yu Huajun, et al. Construction of lung cancer cell lines with stable knockout of ACSS3 gene using CRISPR / Cas9 technology [J]. Basic Medicine and Clinical, 2025, 45(8): 1016-1021.

[0069] The above two ACSS3 K97 mutant genes were inserted into the attR1-attR2 site of the lentiviral vector pLenti CMV Hygro DEST(w117-1) (Addgene, #17454) containing the CMV promoter and hygromycin resistance through Gateway LR recombination reaction to obtain a recombinant lentiviral vector. The constructed recombinant lentiviral vector was co-transfected with the packaging plasmid psPAX2 and the envelope plasmid pMD2.G into HEK293T cells, and the supernatant containing virus particles was collected after 48 hours. After filtration through a 0.45 μm filter, the obtained lentiviral particle supernatant was stored at -80°C for subsequent lentiviral infection. The H460 cells with ACSS3 knocked out were infected with lentivirus to restore the expression of the protein simulating the acetylation modification of the K97 site of ACSS3 and the deacetylation modification of the K97 site of ACSS3. The specific steps are as follows: first, the cells were seeded into a 24-well plate at 2.5x10 5After the cells adhere, replace the fresh complete medium (gibco, RPMI Mediun 1640 basic lx basic medium: fetal bovine serum: penicillin-streptomycin double antibody = 90: 10: 1). Take out the -80℃ frozen lentivirus particle supernatant, melt in ice bath, take out 25 μL of lentivirus plasmid supernatant and add to the cells, gently shake the culture dish to mix, and transfer to the cell culture box for overnight culture.

[0070] After 8-10h of infection, replace the fresh complete medium and continue to culture for 72h, observe the cell state, and if the cell state is good, add 2000 μg / mL concentration of hygromycin B, and act for 7 days, during which the cell state is observed, and if the cell state is good, continue to add hygromycin B; if the cell state is poor, stop adding hygromycin B and replace the liquid to continue to culture, and then add hygromycin B until it acts for 7 days.

[0071] Using the limiting dilution method, H460 cells stably expressing ACSS3 K97 acetylation and ACSS3 K97 deacetylation proteins are screened and obtained. The cell concentration is prepared to be 1×10 4 Cells / mL. First, use the plunger to add 100 μL of complete medium without cells to each well of the 96-well plate, and add 100 μL of complete medium to the first column (except the first well). Then, 200 μL of prepared cell suspension is added to the first well, and 100 μL of the plunger is used to dilute each well in the first column, and then 100 μL of the plunger is used to dilute horizontally. Each well needs to be gently blown for 15-20 times to fully mix the cells. After 4-5 days of culture, the culture plate is taken out, and single growing cells are selected under a microscope and marked. Continue to culture for 10-15 days. When the single clone cell strain grows into a larger cell mass, transfer to a 24-well plate for continuous culture, and then continue to expand the culture in the order of 12-well plate-6-well plate-6cm culture dish. When the cells are expanded to 6cm culture dish, part of the cells are retained for continuous culture, and the other part is used for Western blot detection of ACSS3 expression. Finally, select two cell strains with similar ACSS3 expression, as shown in Figure 4 .

[0072] 2) ACSS3 97 site lysine acetylation modification promotes the proliferation, migration / invasion, and tumorigenic ability of lung cancer cells

[0073] Experimental cells: H460 cells expressing ACSS3 K97 acetylation modification and ACSS3 K97 deacetylation modification proteins

[0074] (1) MTT experiment

[0075] Two strains of cells were inoculated in five 96-well plates at a density of 1000 cells per well, with 6 replicates in each group, and placed in a 37°C carbon dioxide incubator. At 0h, 24h, 48h, 72h and 96h, one plate was taken out, 10% MTT-containing complete medium was added, and it was incubated in the dark for 4h. Then the supernatant was aspirated, 150μL DMSO was added, and it was shaken for 10min. The absorbance was measured at 490nm. Statistical analysis of the data showed that the simulated ACSS3 K97 acetylation modification promoted the proliferation of lung cancer cells, ****: P<0.0001 Figure 5 A).

[0076] (2) Cloning experiment

[0077] Two mutant cells were inoculated in a 6-well plate, 100 cells per well, supplemented with 2mL of complete medium, and placed in a 37°C carbon dioxide incubator. The medium was changed every 3 days. After 14 days, the cells were fixed and stained, washed and dried, and then counted by Image J. Statistical analysis of the data showed that the simulated ACSS3 K97 acetylation modification promoted the clonogenicity of lung cancer cells, ***: P<0.001 Figure 5 B).

[0078] (3) Transwell migration / invasion experiment

[0079] ① Migration experiment

[0080] The cells were starved for 2h. The starved cells were inoculated in the Transwell chamber at a density of 5×10 4 cells / well (600μL of complete medium containing 10% fetal bovine serum was added to the lower chamber), and incubated in a 37°C carbon dioxide incubator for 24h. The chamber was removed, washed twice with PBS, fixed with 4% paraformaldehyde for 30min, aspirated the paraformaldehyde, washed twice with PBS, stained with crystal violet for 8min, washed twice with PBS, and finally gently wiped the cells in the chamber with a cotton swab. The chamber was placed back into the 24-well plate, and after drying, the number of cells that had migrated through the bottom of the chamber was observed under a fluorescence digital photography microscope, photographed and saved, and counted using Image J.

[0081] ② Invasion experiment

[0082] Logarithmic growth phase cells were starved for 24h. Diluted Matrigel was prepared at a ratio of gibco, RPMI Mediun 1640 basic 1x basic medium: Matrigel = 25:1, and 50μL of diluted Matrigel was added to each chamber, and placed in the incubator for 2h. After 2h, the starved cells were removed, and the concentration of 2.5×10 5Chamber, 200 μL cell suspension, 600 μL complete medium, and then transferred to the cell culture incubator for 24 h. After 24 h, the chamber was removed, washed twice with PBS, fixed with 4% paraformaldehyde for 30 min, and then washed twice with PBS. The chamber was then stained with crystal violet for 8 min, washed twice with PBS, and finally the cells in the chamber were gently wiped with a cotton swab. The chamber was then placed back into the 24-well plate and allowed to dry. The number of cells that passed through the bottom of the chamber was observed under a fluorescent digital camera microscope, photographed, and counted using Image J.

[0083] Statistical analysis showed that the simulation of ACSS3 K97 acetylation promoted the migration and invasion of lung cancer cells, ****: P < 0.0001; **: P < 0.001. Figure 6

[0084] (4) Subcutaneous tumor transplantation model experiment in nude mice

[0085] A sufficient number of cells were cultured, washed with PBS, digested, centrifuged, resuspended with basal medium, counted, and adjusted to a cell concentration of 1.25 x 10 7 cells / mL. After centrifugation, the cells were resuspended in basal medium: Matrigel = 3:7, adjusted to a cell concentration of 1.25 x 10 7 cells / mL, and stored on ice. Each nude mouse was subcutaneously injected with 200 μL of the cell suspension, and the state was observed every 3 days, and the long diameter (L) and short diameter (W) of the tumor were measured to calculate the volume (V = L x W 2 / 2). The mice were sacrificed when the tumor volume reached 1000 mm 3 , the tumor mass was photographed and weighed, fixed with 4% paraformaldehyde, and stored at -80°C. The results showed that the simulation of ACSS3 K97 acetylation promoted the growth of lung cancer cells in nude mice, *: P < 0.05. Figure 7

[0086] The above results show that ACSS3 K97 acetylation promotes cell proliferation, migration, and invasion. The above two types of H460 cells with ACSS3 K97 mutations were inoculated in nude mice. The results showed that the simulation of ACSS3 K97 acetylation significantly increased the growth of lung cancer H460 cells in nude mice, and therefore ACSS3 K97 acetylation has the effect of promoting and maintaining the survival and growth of lung cancer cells. ACSS3 K97 acetylation promotes lung cancer growth. Combined Figure 7 ​​Lung cancer H460 cells expressing simulated ACSS3K97 acetylation and simulated ACSS3K97 deacetylation were respectively inoculated into nude mice and fed for 24 days. Tumor tissue was then collected for analysis and comparison. The results showed that the average mass of ACSS3K97 acetylation was 0.454 g, and the average mass of ACSS3K97 deacetylation was 0.756 g. The growth rate of lung cancer cells in the ACSS3K97 acetylation group was significantly faster than that in the ACSS3K97 deacetylation group (P<0.05).

[0087] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. The application of acetylation modification of the lysine residue at position 97 of ACSS3 in the preparation of clinical diagnostic reagents for lung cancer, characterized in that, The amino acid sequence of ACSS3 is shown in SEQ ID NO.

1.

2. A biomarker for the development and progression of lung cancer, characterized in that, The lysine residue at position 97 of ACSS3 is acetylated; the amino acid sequence of ACSS3 is shown in SEQ ID NO.

1.

3. A therapeutic target for lung cancer, characterized in that, The lysine residue at position 97 of ACSS3 is acetylated; the amino acid sequence of ACSS3 is shown in SEQ ID NO.

1.

4. The application of acetylation modification of the lysine residue at position 97 of ACSS3 in the preparation of formulations that promote the growth, proliferation, and / or migration of lung cancer cells, characterized in that, The amino acid sequence of ACSS3 is shown in SEQ ID NO.

1.

5. The application of acetylation modification of the lysine residue at position 97 of ACSS3 in the preparation of anti-lung cancer drugs, characterized in that, The amino acid sequence of ACSS3 is shown in SEQ ID NO.

1.

6. The application of acetylation modification of the lysine residue at position 97 of ACSS3 in the preparation of liver cancer diagnostic reagents or kits, characterized in that, The amino acid sequence of ACSS3 is shown in SEQ ID NO.

1.

7. The application of acetylation modification of the lysine residue at position 97 of ACSS3 in the preparation of cell samples for lung cancer diagnosis or research, characterized in that, The amino acid sequence of ACSS3 is shown in SEQ ID NO.1.

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