Downregulation of microRNA-4295 enhances cisplatin-induced gastric cancer cell apoptosis through the EGFR/PI3K/Akt signaling pathway by targeting LRIG1

• DOI: 10.3892/ijo.2018.4595
• Publication Date: 2018-10-12T10:06:06Z
• Authors: Rong Yan; Kang Li; Da-Wei Yuan; Hao-Nan Wang; Yong Zhang; Cheng-Xue Dang; Kun Zhu
• Keywords: Membrane Potential, Mitochondrial; Membrane Glycoproteins; Cell Survival; Down-Regulation; Articles; 3. Good health; ErbB Receptors; Gene Expression Regulation, Neoplastic; Inhibitory Concentration 50; MicroRNAs; 03 medical and health sciences; 0302 clinical medicine; Stomach Neoplasms; Cell Line, Tumor; Humans; Cisplatin; Phosphatidylinositol 3-Kinase; 3' Untranslated Regions; Proto-Oncogene Proteins c-akt; Cell Proliferation; Signal Transduction

Gastric cancer (GC) is one of the leading causes cancer-associated mortality worldwide. The aim present study was to investigate mechanism microRNA-4295 (miR-4295), which regulates cisplatin (DDP)-induced apoptosis in GC cells through leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1)-mediated epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Two cell lines were selected, with highest expression miR-4295 lowest LRIG1, for experiments. half maximal inhibitory concentration DDP human MKN-28 MKN-45 calculated, mitochondrial membrane potentials detected by tetramethylrhodamine, ethyl ester, perchlorate staining. proliferation or without treatment assessed MTT assay plate colony formation, as well flow cytometry TUNEL Western blot analysis reverse transcription-quantitative polymerase chain reaction employed determine EGFR/PI3K/Akt pathway-related genes apoptosis-related genes. LRIG1 identified a target gene miR-4295. upregulated, downregulated cells. Furthermore, enhanced decrease increase promoted inhibited DDP-induced treatment. In addition, increased levels EGFR, PI3K, Akt, p-PI3K p-Akt, suggesting that promotes activation pathway targeting LRIG1. targeted negatively regulated activate pathway, thereby promoting inhibiting induced DDP. Therefore, may be novel therapeutic patients GC.