Abstract：Objective: To investigate the interaction between cohesive protein 1 (Numb1) and integrin β1 (ITGB1) on gastric cancer progression and drug resistance and its related mechanisms. Methods: The expression levels of Numb1 and ITGB1 in tumors and adjacent tissues of 21 patients with gastric cancer were detected by qRT-PCR, and the correlation between the expression levels of Numb1 and ITGB1 was analyzed. The overexpressed vectors (flag-Numb1, flag-ITGB1, and flag-NC) were transfected into BGC-823 cells by lentivirus, and the binding sites of Numb1 and ITGB1 were detected by the immunoprecipitation method. si-NC, si-Numb1, and si-ITGB1 were transfected into BGC-823 cells. The mRNA expression levels of Numb1 and ITGB1 were detected by qRT-PCR and the protein expression levels of Numb1 and ITGB1 were detected by Western blot. CCK8 detected cell proliferation and sensitivity to oxaliplatin, cell migration was detected by cell scratch assay, and cell invasion was detected by Transwell. Results: The expression levels of Numb1 and ITGB1 were elevated in tumor tissues compared to paraneoplastic tissues (P<0.05), and Numb1 was positively correlated with ITGB1 expression levels (r=0.6270). In cellular assays, ITGB1 protein was detected in the immunoprecipitation products of flags overexpressing flag-Numb1, and Numb1 protein was detected in the immunoprecipitation products of flags overexpressing flag-ITGB1. Compared with the si-NC group, the si-Numb1 group showed reduced levels of Numb1 and ITGB1 mRNA and protein expression (P<0.05), reduced cell proliferation (P<0.05), increased sensitivity to oxaliplatin (P<0.05), and reduced cell migration and invasion (P<0.05). Compared with the si-NC group, the si-ITGB1 group showed reduced ITGB1 mRNA and protein expression levels (P<0.05), reduced cell proliferation (P<0.05), increased sensitivity to oxaliplatin (P<0.05) and reduced cell migration and invasion (P<0.05). Conclusion: Numb1 regulates ITGB1 expression levels through interaction with ITGB1 and promotes proliferation, migration, invasion and resistance to chemotherapeutic agents in gastric cancer cells
陈勇, 何冬雷, 周江浩, 梁月祥, 杨丞. Numb1与ITGB1的相互作用在胃癌恶化和耐药中的调控机制研究[J]. 河北医学, 2022, 28(9): 1420-1424.
CHEN Yong, HE Donglei, ZHOU Jianghao, et al. Study of the Regulatory Mechanism of the Interaction Between Numb1 and ITGB1 in Gastric Cancer Progression and Drug Resistance. HeBei Med, 2022, 28(9): 1420-1424.
[1] Hsieh HL,Yu MC,Cheng LC,et al.Molecular mechanism of therapeutic approaches for human gastric cancer stem cells[J].World Stem Cells,2022,14(1):76-91. [2] Wan WB,Kong QL.Knockdown of long noncoding RNA linc-ITGB1 inhibits tumor metastasis in colorectal cancer through suppressing BDNF[J].Eur Rev Med Pharmacol Sci,2020,24(14):7551. [3] Lin YC,Ohbayashi N,Hongu T,et al.Arf6 in lymphatic endothelial cells regulates lymphangiogenesis by controlling directional cell migration[J].Sci Rep,2017,7(1):11431. [4] Kudinov AE,Karanicolas J,Golemis EA,et al.Musashi RNA-binding proteins as cancer drivers and novel therapeutic targets[J].Clin Cancer Res,2017,23(9):2143-2153. [5] Karaczyn AA,Adams TL,Cheng RY,et al.Human NUMB6 induces epithelial-mesenchymal transition and enhances breast cancer cells migration and invasion[J].Cell Biochem,2017,118(2):237-251. [6] Yang Y,Li L,He H,et al,Chen W.Numb inhibits migration and promotes proliferation of colon cancer cells via RhoA/ROCK signaling pathway repression[J].Exp Cell Res,2022,411(2):113004. [7] Liu Z,Luo C,Yang W,et al.Increased Numb protein expression predicts poor clinical outcomes in esophageal squamous cell carcinoma patients[J].Cancer Biol Ther,2018,19(1):34-41. [8] Huaman J,Naidoo M,Zang X,et al.Fibronectin regulation of integrin B1 and SLUG in circulating tumor cells[J].Cells,2019,8(6):618. [9] Oshita F,Kameda Y,Hamanaka N,et al.High expression of integrin beta1 and p53 is a greater poor prognostic factor than clinical stage in small-cell lung cancer[J].Am Clin Oncol,2004,27(3):215-219. [10] Martinez-Morales JR,Cavodeassi F,Bovolenta P.Coordinated morphogenetic mechanisms shape the vertebrate eye[J].Front Neurosci,2017,11:721. [11] Xu E,Zhu H,Wang F,et al.OSI-027 alleviates oxaliplatin chemoresistance in gastric cancer cells by suppressing P-gp induction[J].Curr Mol Med,2021,21(10):922-930.
2022, Vol. 28 
冀公网安备13080202000677号