Abstract：Objective: To investigate the expression level of LYN in gastric cancer and the effect and mechanism of knockdown LYN expression on proliferation and apoptosis of gastric cancer cells.Methods: Immunohistochemistry was used to detect LYN expression in gastric cancer and adjacent tissues.Shrna-LYN was transfected into AGS (gastric adenocarcinoma) cells using Lipofectamine 2000, and untransfected gastric cancer cells were used as control. CCK8 and flow cytometry were used to detect the effects of LYN knockdown on AGS cell proliferation and apoptosis, respectively.Western blot analysis was used to investigate the changes in the expression levels of AKT/mTOR signaling pathway related proteins and apoptosis related proteins Bcl2, Bax, Caspase9 and Casapse3 induced by LYN knockdown, and to study its proliferation and apoptosis mechanism.Bioinformatics software was used to screen out the target gene miR-496, and western blot was used to detect the effect of transfection miR-496 on LYN expression. Rescue experiments were performed to analyze the interaction between miR-496 and LYN. Results: The sample number of LYN overexpression in gastric cancer tissues was 58 cases, which was significantly higher than that in paracancer tissues (28 cases) (P<0.05). After transfection 48 and 72h, the absorbance values of sh-LYN group were (0.0992±0.0346) and (1.0953±0.0379), which were significantly lower than those of NC group (1.4123±0.1161) and (1.6717±0.0120),(P<0.05).After transfection, the apoptosis rate of sh-LYN group (16.3567±0.5556) was significantly higher than that of NC group (P<0.05). After LYN knockdown, the expression levels of Bcl2 (0.4629 ± 0.0294), P-Akt (0.5565 ± 0.0473), P-MTOR (0.6167 ± 0.0459) and p70S6K (0.6049 ± 0.0570) decreased compared with NC control group. The expression of Bax (1.407 ± 0.0528), Caspase-9 (1.5200 ± 0.1063), caspase-3 (1.4170 ± 0.0751) increased. Transfection of miR-496 could inhibit LYN expression in AGS cells. Conclusion: Knockdown LYN expression can inhibit AKT/mTOR signaling pathway, thereby inhibiting proliferation and promoting apoptosis of gastric cancer cells, and its effect on gastric cancer cells is regulated by miR-496.
苏锐, 李英健, 刘鹏, 赵恩宏. LYN通过AKT/mTOR信号通路对胃癌细胞增值及凋亡的影响[J]. 河北医学, 2022, 28(8): 1256-1261.
SU Rui, LI Yingjian, LIU Peng, et al. Effects of LYN on Proliferation and Apoptosis of Gastric Cancer Cells through AKT/mTOR Signaling Pathway. HeBei Med, 2022, 28(8): 1256-1261.
[1] Denis O O,Lucas J A,Brian J D,et al.Lyn regulates creatine uptake in an imatinib-resistant CML cell line[J].BBA-General Subjects,2020,1864(4):129507. [2] Rui Su,Enhong Zhao,Jun Zhang.miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer[J].Open Medicine,2021,16(1):1206-1214. [3] Nakauchi M,Suda K,Shibasaki S,et al.Prognostic factors of minimally invasive surgery for gastric cancer:Does robotic gastrectomy bring oncological benefit[J].World Gastroenterol,2021,27(39):6659-6672. [4] Wong M C S,Huang J,Chan P S F,et al.Global Incidence and mortality of gastric cancer,1980-2018[J].JAMA network open,2021,4(7):e2118457. [5] Martellucci S,Clementi L,Sabetta S,et al.Src family kinases as therapeutic targets in advanced solid tumors:what we have learned so far[J].Cancers,2020,12(6):1448. [6] Zhang Q,Meng X,Qin G,et al.Lyn kinase promotes the proliferation of malignant melanoma cells through inhibition of apoptosis and autophagy via the PI3K/Akt signaling pathway[J].Cancer,2019,10(5):1197-1208. [7] Meng L,Chen Z,Jiang Z,et al.MiR-122-5p suppresses the proliferation,migration,and invasion of gastric cancer cells by targeting LYN[J].Acta Biochim Biophys Sin (Shanghai),2020,52(1):49-57. [8] Xu F,Na L,Li Y,et al.Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours[J].Cell Biosci,2020,10(1):54. [9] Lin J,Fang Y,Zhang M,et al.Phosphorylation of PRAS40 contributes to the activation of the PI3K/AKT/mTOR signaling pathway and the inhibition of autophagy following status epilepticus in rats[J].Experimental and Therapeutic Medicine,2020,20(4):3625-3632. [10] Erdal M E,Gorucu Y S,Ay M E,et al.A study investigating the role of 2 candidate SNPs in bax and Bcl-2 genes in alzheimer's disease[J].P R Health Sci J,2020,39(3):264-269. [11] Dhani S,Zhao Y,Zhivotovsky B.A long way to go:caspase inhibitors in clinical use[J].Cell Death Dis,2021,12(10):949. [12] Ma R,Zhu P,Liu S,et al.miR-496 suppress tumorigenesis via targeting BDNF-mediated PI3K/Akt signaling pathway in non-small cell lung cancer[J].Biochem Biophys Res Commun,2019,518(2):273-277. [13] Parker M S,Balasubramaniam A,Sallee F R,et al.Fragmentation and matching of human microRNA sequences in 3'utr[J].Microrna,2020,9(5):378-394.
2022, Vol. 28 
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