PTPRG-AS1 regulates the KITLG/KIT pathway through the ceRNA axis to promote the malignant progression of gastric cancer and the intervention effect of Compound Kushen injection on it

• Published in: Pharmacological research Vol. 215; p. 107743
• Main Authors: Wu, Chao, Gao, Yifei, Jin, Zhengsen, Huang, Zhihong, Wang, Haojia, Lu, Shan, Guo, Siyu, Zhang, Fanqin, Zhang, Jingyuan, Huang, Jiaqi, Tao, Xiaoyu, Liu, Xinkui, Zhang, Xiaomeng, You, Leiming, Li, Qinglin, Wu, Jiarui
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.05.2025; Elsevier
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Cell Line, Tumor; Cell Proliferation - drug effects; Compound Kushen injection; Disease Progression; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Gastric cancer; Gene Expression Regulation, Neoplastic - drug effects; Hsa-miR-421; Humans; KITLG; Male; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; PTPRG-AS1; RNA, Competitive Endogenous; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction - drug effects; Stem Cell Factor - genetics; Stem Cell Factor - metabolism; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; IHC; PFA; Compound Kushen injection; SsGSEA; BSA; PFI; RBC; TUNEL; DEmRNAs; IC50; MREs; CCK-8; KEGG; MF; MiRNAs; UPLC-Q/TOF-MSE; CeRNA; RT-qPCR; Gastric cancer; HGB; NSG; DSS; DEmiRNAs; LncRNAs; GMP; EMT; TCA; NC; HCT; Hsa-miR-421; MRNA; MET; ELISA; TCM; DElncRNAs; PCT; SRB; MRI; PPI; BP; PTPRG-AS1; DEGs; NMPA; OD; CD117; PLT; WBC; ESI; GC; WT; CC; CKI; OS; GO; QPCR; NcRNA; KITLG; EdU; SCF; TMT; DEPs; CNScore; HER2; NEU
• ISSN: 1043-6618; 1096-1186; 1096-1186
• DOI: 10.1016/j.phrs.2025.107743

Gastric cancer (GC) is a common malignant tumor with high mortality, recurrence, and metastasis rates. Compound Kushen injection (CKI) combination chemotherapy has been clinically used for the treatment of GC in China for many years, but its underlying mechanisms of action remain unclear. Recent reports have highlighted the important role of the competing endogenous RNA (ceRNA) mechanism of noncoding RNA (ncRNA) and messenger RNA (mRNA) formation in GC and other tumors. This study aimed to investigate the effects of CKI on GC from the ceRNA perspective. We confirmed the inhibitory effect of CKI on GC in mouse models and cell lines. By examining the GC cell lines sensitive to CKI treatment, we developed the CNScore method to analyze the ceRNA network, revealing that the CKI-GC ceRNA network promotes GC proliferation and metastasis through the PTPRG-AS1/hsa-miR-421/KITLG axis. Finally, we constructed GC cell models with PTPRG-AS1 overexpression or knockdown and GC liver metastasis models and found that PTPRG-AS1 can sponge hsa-miR-421, releasing KITLG and promoting GC proliferation and metastasis through the KITLG/KIT pathway. Taken together, CKI can suppress these malignant phenotypes by regulating the PTPRG-AS1/hsa-miR-421/KITLG axis. [Display omitted] •Lnc RNA PTPRG-AS1 functions as a sponge for hsa-miR-421, thereby releasing KITLG and activating the KITLG/KIT pathway, which promotes the growth, proliferation, and metastasis of gastric cancer.•Compound Kushen injection inhibits the progression of gastric cancer by targeting the PTPRG-AS1/hsa-miR-421/KITLG axis through the suppression of the ceRNA network.•The ceRNA Network Score (CNScore) method was utilized to analyze and annotate the ceRNA network, thereby providing a more coherent interpretation of its biological significance.