|
|
The Expression of PNMA 5 in Gastric Cancer Tissues and its Relationship with the Malignant Biological Behaviors of Gastric Cancer Cells |
HUANG Lihua, ZUO Yi, WEI Zhenping, et al |
The No.923rd Hospital of the Joint Logistic Support Force of the People's Liberation Army of China, Guangxi Nanning 530011, China |
|
|
Abstract Objective: To investigate the expression of paraneoplastic antigen Ma family member 5 (PNMA5) in gastric cancer (GC) and its relationship with GC cells' proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Methods: Cancerous and paracancerous tissue sections from 42 GC patients were collected, and the expression of PNMA was detected by immunohistochemical staining. The GC cell lines SGC-7901, HGC27, N87,NU1, BGC-823, and the human normal gastric mucosal epithelial cell line GES-1 were cultured, and the expression level PNMA5 was detected by Western blot. Stable overexpression of PNMA5 in N87 cells (PNMA5-OE-N87) and negative control cells (PNMA5-OENC-N87), as well as stable knockdown of PNMA5 in HGC27 cells (shPN5-HGC27) and its negative control cells (shPNMA5-NC-HGC27) were constructed by lentivirus transfection. Subsequently the proliferation activity of each group of cells was detected by CCK-8 assay and colony formation assay, the migration activity of each group of cells was detected by assay, the invasive activity of each group of cells was detected by Transwell assay, and the expression levels of EMT-related proteins Vimentin, E-cherin, and N-cadherin were detected by Western blot. The nude mouse GC xenograft models were constructed to observe the effect of PNMA overexpression or knockdown on tumor growth and EMT level in vivo. Results: Compared with adjacent tissues, PNMA5 was upregulated in cancer tissues (P<0.05). Compared with ES-1 cells, PNMA5 was upregulated in all GC cell lines (all P<0.05). Compared with PNMA5-OENC-N87 cells, PNMA5-OE-N87 cells had significantly increased proliferation, migration, and invasion activities, with elevated Vimentin and N-cherin expression levels and reduced E-cadherin expression level (all P<0.05); compared with shPNMA5-NC-H27 cells, shPNMA5-HGC27 cells had significantly reduced proliferation, migration, and invasion activities, with reduced Vimentin and N-cherin expression levels and elevated E-cadherin expression level (all P<0.05). In vivo experiments showed that overexpression of PN5 promoted GC tumor growth and EMT level, while knockdown of PNMA5 inhibited tumor growth and EMT level(all P<0.05). Conclusion: PNMA5 is upregulated in GC and promotes GC cells proliferation, migration, invasion, and EMT, acting as an oncogene in GC.
|
|
|
|
|
[1] Smyth EC,Nilsson M,Grabsch HI,et al.Gastric cancer[J].Lancet,2020,396(10251):635-648. [2] Ajani JA,D'Amico TA,Bentrem DJ,et al.Gastric cancer,version 2.2022,NCCN clinical practice guidelines in oncology[J].Natl Compr Canc Netw,2022,20(2):167-192. [3] Patel TH,Cecchini M.Targeted therapies in advanced gastric cancer[J].Curr Treat Options Oncol,2020,21(9):70. [4] Lischer C,Eberhardt M,Flamann C,et al.Gene network-based and ensemble modeling-based selection of tumor-associated antigens with a predicted low risk of tissue damage for targeted immunotherapy[J].Immunother Cancer,2024,12(5):8104. [5] Wang X,Liu S,Shao Z,et al.Bioinformatic analysis of the potential molecular mechanism of PAK7 expression in glioblastoma[J].Mol Med Rep,2020,22(2):1362-1372. [6] Liu Y,Chen Z,You J,et al.Paraneoplastic Ma antigen 5 promotes cellular processes of primary cells in ovarian endometriosis[J].Afr Reprod Health,2025,29(4):37-48. [7] Anderson HJ,Huang S,Lee JB.Paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome:part I.clinical overview and pathophysiology[J].Am Acad Dermatol,2024,91(1):1-10. [8] Zhou Y,Zang Y,Yang Y,et al.Candidate genes involved in metastasis of colon cancer identified by integrated analysis[J].Cancer Med,2019,8(5):2338-2347. [9] Lee YH,Pang SW,Poh CL,et al.Distinct functional domains of PNMA5 mediate protein-protein interaction,nuclear localization,and apoptosis signaling in human cancer cells[J].Cancer Res Clin Oncol,2016,142(9):1967-1977. [10] Yu Z,Huang H,Yi X,et al.EMT (epithelial-mesenchymal transition) in gastric cancer identifies prognostic and immunotherapeutically relevant gene signatures[J].Asian Surg,2021,44(5):792-793. [11] Zhao Z,Zhu Y.FAP,CD10,and GPR77-labeled CAFs cause neoadjuvant chemotherapy resistance by inducing EMT and CSC in gastric cancer[J].BMC Cancer,2023,23(1):507. [12] Lin J,Zhang X,Meng F,et al.PNMA5 accelerated cellular proliferation,invasion and migration in colorectal cancer[J].Am Transl Res,2022,14(4):2231-2243. |
|
|
|