Jinxin Feng1, Kejun Li1, Gaojie Liu1, Yanlin Feng1, Huijuan Shi2, Xiangliang Zhang3. 1. Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China. 2. Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, PR China. Electronic address: hjshi18@163.com. 3. Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Hengzhigang Road 78#, Guangzhou, 510095, Guangdong, China. Electronic address: zhxlgmu@163.com.
Abstract
BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is widely used for clinical treatment of advanced cancers. However, the regulatory mechanism underlying precise hyperthermia treatment in advanced gastric cancer (AGC) remains unclear. MiR-409-3p is reportedly downregulated in a variety of cancers, although its role in regulating treatment of AGC by precise hyperthermia remains unclear. The underlying mechanisms of miRNA-medicated regulation have been investigated using predicted and validated miRNA-gene targets, confirming the role of miRNA in HIPEC; METHODS: We used quantitative real time PCR (qRT-PCR) to detect miR-409-3p expression in gastric cancer (GC), as well as adjacent normal tissues, following exposure to varying temperatures. We detected miR-409-3p targets using dual-luciferase assay, then performed cell apoptosis, western blotting, invasion, and migration assays to detect GC functions; RESULTS: MiR-409-3p was upregulated and downregulated in precise hyperthermia and AGC, respectively. Moreover, miR-409-3p upregulated the Krüppel-like-factor 17 (KLF17), which subsequently inhibited migration, invasiveness, and epithelial-mesenchymal transition (EMT) but promoted apoptosis in GC cells; CONCLUSIONS: Precise hyperthermia upregulated miR-409-3p and KLF17 indirectly, thereby inhibiting invasion, migration, and EMT, and promoting apoptosis of gastric cancer cells.
BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is widely used for clinical treatment of advanced cancers. However, the regulatory mechanism underlying precise hyperthermia treatment in advanced gastric cancer (AGC) remains unclear. MiR-409-3p is reportedly downregulated in a variety of cancers, although its role in regulating treatment of AGC by precise hyperthermia remains unclear. The underlying mechanisms of miRNA-medicated regulation have been investigated using predicted and validated miRNA-gene targets, confirming the role of miRNA in HIPEC; METHODS: We used quantitative real time PCR (qRT-PCR) to detect miR-409-3p expression in gastric cancer (GC), as well as adjacent normal tissues, following exposure to varying temperatures. We detected miR-409-3p targets using dual-luciferase assay, then performed cell apoptosis, western blotting, invasion, and migration assays to detect GC functions; RESULTS:MiR-409-3p was upregulated and downregulated in precise hyperthermia and AGC, respectively. Moreover, miR-409-3p upregulated the Krüppel-like-factor 17 (KLF17), which subsequently inhibited migration, invasiveness, and epithelial-mesenchymal transition (EMT) but promoted apoptosis in GC cells; CONCLUSIONS: Precise hyperthermia upregulated miR-409-3p and KLF17 indirectly, thereby inhibiting invasion, migration, and EMT, and promoting apoptosis of gastric cancer cells.