The promoting effect of upregulated expression of AHCY in lung cancer on cancer cell proliferation and the impact mechanism of MAT1A expression_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LIANG Yueya ^1,2 ,  HUANG Jian ^1,3

1. Department of Pathology, School of Basic Medicine, Guangdong Medical University, Zhanjiang, Guangdong 524000, P. R. China;
2. Department of Pathology, Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, P. R. China;
3. Pathological Diagnosis and Research Center of Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524000, P. R. China;

Corresponding?author：

HUANG Jian, Email: 18665763598@163.com

Keywords：

S-adenosyl-homocysteine hydrolase; lung cancer; methionine adenosyltransferase 1A; S-adenosylmethionine; methylation; cell proliferation; apoptosis

DOI：

10.7507/1671-6205.202510067

Video：

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Objective To investigate the promoting effect of S-adenosyl-homocysteine hydrolase (AHCY) on the proliferation of lung cancer cells and its regulatory mechanism on the expression of methionine adenosyltransferase 1A (MAT1A). Methods Wayne plot analysis was performed on four lung cancer data chips, including GSE103512, GSE18842, GSE20189, and GSE102286, to screen for differentially expressed key genes. Protein immunoprecipitation assay was used to detect the interaction between AHCY and MAT1A. pAdTrack-CMV-NC+pCV702-NC (NC), pAdTrack-CMV, and pAdTrack-CMV+pCV702 were transfected into A549 and PC9 cells, respectively. The cell proliferation, apoptosis, the mitochondrial membrane potential, the ROS levels in cells, the total RNA methylation levels in cells, and the expression of AHCY and MAT1A in cells were detected, sequentially. Results The statistical analysis identified AHCY and MAT1A were the key differentially expressed genes across the four datasets. Co-immunoprecipitation experiments confirmed a direct interaction between AHCY and MAT1A in lung cancer (P<0.05). Upregulation of the expression of AHCY could significantly increase the proliferation of A549 and PC9 cells, decrease the cell apoptosis, increase the mitochondrial membrane potential, alleviate the intracellular reactive oxygen species levels, and decrease the total RNA methylation levels, while MAT1A overexpression partially reversed the promoting effects of AHCY on lung cancer cells. All differences were statistically significant (all P<0.05). Conclusions The expression of AHCY is significantly increased in lung cancer, while the expression of MAT1A is significantly decreased in lung cancer. High expression of AHCY can promote the cancer cell proliferation and affect total RNA methylation, while downregulate the expression of MAT1A in lung cancer cells.

Citation： LIANG Yueya, HUANG Jian. The promoting effect of upregulated expression of AHCY in lung cancer on cancer cell proliferation and the impact mechanism of MAT1A expression. Chinese Journal of Respiratory and Critical Care Medicine, 2026, 25(5): 326-335. doi: 10.7507/1671-6205.202510067 Copy

1.	Li J, Zhang D, Wang S, et al. Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancer. J Adv Res, 2025, 68(2): 341-357.
2.	Lucas O, Ward S, Zaidi R, et al. Characterizing the evolutionary dynamics of cancer proliferation in single-cell clones with SPRINTER. Nat Genet, 2025, 57(1): 103-114.
3.	Fu NJ, Sheng YW, Fan Z, et al. Synthetic lethality of SHP2 and XIAP suppresses proliferation and metastasis in KRAS-mutant nonsmall cell lung cancer. Adv Sci (Weinh), 2025, 12(15): e2411642.
4.	Li Y, Hu G, Huang F, et al. MAT1A suppression by the CTBP1/HDAC1/HDAC2 transcriptional complex induces immune escape and reduces ferroptosis in hepatocellular carcinoma. Lab Invest, 2023, 103(8): 100180.
5.	Tellai AD, Haghnejad V, Antoine J, et al. The complex post-transcriptional regulation of genes coding for methionine adenosyl transferase: New insights for liver cancer. Biochimie, 2025, 9(3): 9084-9087.
6.	Xu H, Zhao Q, Cai D, et al. o8G-modified circKIAA1797 promotes lung cancer development by inhibiting cuproptosis. J Exp Clin Cancer Res, 2025, 44(1): 110.
7.	Feng S, Zhang L, Sun T, et al. OVOL1 Promotes proliferation and metastasis of non-small cell lung cancer by regulating APOE-mediated cholesterol metabolism. J Cell Mol Med, 2025, 29(11): e70634.
8.	Fan H, Xu P, Zou B, et al. Isoquercitrin inhibits lung cancer cell growth through triggering pyroptosis and ferroptosis. Nutr Cancer, 2025, 77(2): 299-310.
9.	Guo T, Liu L, Zeng L, et al. GMPS inhibits the proliferation and migration of non-small cell lung cancer via the regulation of the DNMT 1/SERPINB2 axis. Cell Oncol (Dordr), 2025, 48(4): 1145-1158.
10.	Mi J, Zhang W, Ren Y, et al. Neuronal guanine nucleotide exchange factor promotes the axonal growth and cancer cell proliferation via Ephrin-A3/EphA2 axis in lung adenocarcinoma. J Transl Med, 2025, 23(1): 246.
11.	Tian C, Li C, Wang J, et al. ADAR1 enhances tumor proliferation and radioresistance in non-small cell lung cancer by interacting with Rad18. Cell Oncol (Dordr), 2025, 48(2): 471-485.
12.	Shi G, Wei J, Rahemu S, et al. Study on the regulatory mechanism of luteolin inhibiting WDR72 on the proliferation and metastasis of non small cell lung cancer. Sci Rep, 2025, 15(1): 12398.
13.	Wei J, Lei G, Chen Q, et al. Casticin inhibits proliferation of Non-small cell lung cancer cells through regulating reprogramming of glucose metabolism. Phytomedicine, 2025, 136(1): 156278.
14.	Lei M, Yeung YT, Nie W, et al. AHCYL1 mediates the tumor-promoting effect of PREX2 in non-small cell lung carcinoma. Theranostics, 2025, 15(12): 5772-5789.
15.	Jin G, Song Y, Yan M, et al. STIP1 drives metabolic reprogramming in esophageal squamous cell carcinoma via AHCY-LDHA axis. Exploration (Beijing), 2025, 5(5): 20240198.
16.	Zheng Y, Li Y, Lu M, et al. Baicalein specifically suppresses microsatellite instability colorectal cancer by targeting adenosylhomocysteinase to inhibit histone H3 lysine 4 trimethylation-mediated cancer stemness. Phytomedicine, 2025, 148(9): 157291.
17.	Niu S, Zheng X, Yao Y, et al. The role of AHCY expression in bladder urothelial carcinoma: a bioinformatics and experimental analysis. Cancer Manag Res, 2025, 7(3): 661-673.
18.	Dondajewska E, Allepuz-Fuster P, Maurizy C, et al. Loss of STARD7 triggers metabolic reprogramming and cell cycle arrest in breast cancer. Adv Sci (Weinh), 2025, 12(31): e03022.
19.	Zhang J, Wang P, Li T, et al. Exploration of RNA-binding proteins identified RPS27 as a potential regulator associated with Kaposi's sarcoma development. BMC Cancer, 2025, 25(1): 362.
20.	Shen S, Liu R, Huang J, et al. MAT1A activation of glycolysis to promote NSCLC progression depends on stabilizing CCND1. Cell Death Dis, 2024, 15(10): 768.
21.	Zhou M, Ge X, Xu X, et al. A hot and cold tumor-related prognostic signature for stage II colorectal cancer. Oncol Lett, 2024, 28(3): 419.
22.	Fan W, Cao D, Yang B, Wang J, et al. Hepatic prohibitin 1 and methionine adenosyltransferase α1 defend against primary and secondary liver cancer metastasis. J Hepatol, 2024, 80(3): 443-453.

1. Li J, Zhang D, Wang S, et al. Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancer. J Adv Res, 2025, 68(2): 341-357.
2. Lucas O, Ward S, Zaidi R, et al. Characterizing the evolutionary dynamics of cancer proliferation in single-cell clones with SPRINTER. Nat Genet, 2025, 57(1): 103-114.
3. Fu NJ, Sheng YW, Fan Z, et al. Synthetic lethality of SHP2 and XIAP suppresses proliferation and metastasis in KRAS-mutant nonsmall cell lung cancer. Adv Sci (Weinh), 2025, 12(15): e2411642.
4. Li Y, Hu G, Huang F, et al. MAT1A suppression by the CTBP1/HDAC1/HDAC2 transcriptional complex induces immune escape and reduces ferroptosis in hepatocellular carcinoma. Lab Invest, 2023, 103(8): 100180.
5. Tellai AD, Haghnejad V, Antoine J, et al. The complex post-transcriptional regulation of genes coding for methionine adenosyl transferase: New insights for liver cancer. Biochimie, 2025, 9(3): 9084-9087.
6. Xu H, Zhao Q, Cai D, et al. o8G-modified circKIAA1797 promotes lung cancer development by inhibiting cuproptosis. J Exp Clin Cancer Res, 2025, 44(1): 110.
7. Feng S, Zhang L, Sun T, et al. OVOL1 Promotes proliferation and metastasis of non-small cell lung cancer by regulating APOE-mediated cholesterol metabolism. J Cell Mol Med, 2025, 29(11): e70634.
8. Fan H, Xu P, Zou B, et al. Isoquercitrin inhibits lung cancer cell growth through triggering pyroptosis and ferroptosis. Nutr Cancer, 2025, 77(2): 299-310.
9. Guo T, Liu L, Zeng L, et al. GMPS inhibits the proliferation and migration of non-small cell lung cancer via the regulation of the DNMT 1/SERPINB2 axis. Cell Oncol (Dordr), 2025, 48(4): 1145-1158.
10. Mi J, Zhang W, Ren Y, et al. Neuronal guanine nucleotide exchange factor promotes the axonal growth and cancer cell proliferation via Ephrin-A3/EphA2 axis in lung adenocarcinoma. J Transl Med, 2025, 23(1): 246.
11. Tian C, Li C, Wang J, et al. ADAR1 enhances tumor proliferation and radioresistance in non-small cell lung cancer by interacting with Rad18. Cell Oncol (Dordr), 2025, 48(2): 471-485.
12. Shi G, Wei J, Rahemu S, et al. Study on the regulatory mechanism of luteolin inhibiting WDR72 on the proliferation and metastasis of non small cell lung cancer. Sci Rep, 2025, 15(1): 12398.
13. Wei J, Lei G, Chen Q, et al. Casticin inhibits proliferation of Non-small cell lung cancer cells through regulating reprogramming of glucose metabolism. Phytomedicine, 2025, 136(1): 156278.
14. Lei M, Yeung YT, Nie W, et al. AHCYL1 mediates the tumor-promoting effect of PREX2 in non-small cell lung carcinoma. Theranostics, 2025, 15(12): 5772-5789.
15. Jin G, Song Y, Yan M, et al. STIP1 drives metabolic reprogramming in esophageal squamous cell carcinoma via AHCY-LDHA axis. Exploration (Beijing), 2025, 5(5): 20240198.
16. Zheng Y, Li Y, Lu M, et al. Baicalein specifically suppresses microsatellite instability colorectal cancer by targeting adenosylhomocysteinase to inhibit histone H3 lysine 4 trimethylation-mediated cancer stemness. Phytomedicine, 2025, 148(9): 157291.
17. Niu S, Zheng X, Yao Y, et al. The role of AHCY expression in bladder urothelial carcinoma: a bioinformatics and experimental analysis. Cancer Manag Res, 2025, 7(3): 661-673.
18. Dondajewska E, Allepuz-Fuster P, Maurizy C, et al. Loss of STARD7 triggers metabolic reprogramming and cell cycle arrest in breast cancer. Adv Sci (Weinh), 2025, 12(31): e03022.
19. Zhang J, Wang P, Li T, et al. Exploration of RNA-binding proteins identified RPS27 as a potential regulator associated with Kaposi's sarcoma development. BMC Cancer, 2025, 25(1): 362.
20. Shen S, Liu R, Huang J, et al. MAT1A activation of glycolysis to promote NSCLC progression depends on stabilizing CCND1. Cell Death Dis, 2024, 15(10): 768.
21. Zhou M, Ge X, Xu X, et al. A hot and cold tumor-related prognostic signature for stage II colorectal cancer. Oncol Lett, 2024, 28(3): 419.
22. Fan W, Cao D, Yang B, Wang J, et al. Hepatic prohibitin 1 and methionine adenosyltransferase α1 defend against primary and secondary liver cancer metastasis. J Hepatol, 2024, 80(3): 443-453.

Chinese Journal of Respiratory and Critical Care Medicine

The promoting effect of upregulated expression of AHCY in lung cancer on cancer cell proliferation and the impact mechanism of MAT1A expression

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