Zongqiang Hu1, Yanfeng Yin2, Jie Jiang1, Chuntao Yan2, Yiting Wang2, Dongdong Wang1, Li Li1. 1. Hepato-Pancreato-Biliary Surgery Department, The First People's Hospital of Kunming & The Calmette Affiliated Hospital of Kunming Medical University, Kunming, China. 2. The Central Laboratory, The First People's Hospital of Kunming & The Calmette Affiliated Hospital of Kunming Medical University, Kunming, China.
Abstract
Background: Most patients with hepatitis B virus (HBV) infection will develop hepatocellular carcinoma (HCC). This study aimed to explore the potential mechanism of miR-142-3p in HCC caused by HBV infection. Methods: HepG2 cells and M1 macrophages were cocultured and then infected with HBV to establish an in vitro model. MicroRNA (miRNA) and messenger RNA (mRNA) expression was analyzed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The protein expressions of COX2, ACSL4, PTGS2, GPX4, and NOX1 were analyzed by Western blot. Flow cytometry and TUNEL assays were used to assess cell reactive oxygen species (ROS) and ferroptosis, respectively. Cell invasion and migration were measured by Transwell assay. To evaluate the ferroptosis of M1-type macrophages, glutathione (GSH), malondialdehyde (MDA), and Fe2+ content was detected by corresponding kits. Dual luciferase reporter gene detection verified the targeting relationship between miR-142-3p and SLC3A2. Results: MiR-142-3p was highly expressed in HBV-infected HCC patients and HBV-infected M1-type macrophages. Inhibition of miR-142-3p or overexpression of SLC3A2 reversed ferroptosis and inhibited the proliferation, migration, and invasion of HCC cells. Conclusions: Our findings indicated that miR-142-3p promoted HBV-infected M1-type macrophage ferroptosis through SLC3A2, affecting the production of GSH, MDA, and Fe2+ and accelerating the development of HCC. The regulation of miR-142-3p and its target genes will help to clarify the pathogenesis of HCC induced by HBV infection and provide new theoretical foundations and therapeutic targets. 2022 Journal of Gastrointestinal Oncology. All rights reserved.
Background: Most patients with hepatitis B virus (HBV) infection will develop hepatocellular carcinoma (HCC). This study aimed to explore the potential mechanism of miR-142-3p in HCC caused by HBV infection. Methods: HepG2 cells and M1 macrophages were cocultured and then infected with HBV to establish an in vitro model. MicroRNA (miRNA) and messenger RNA (mRNA) expression was analyzed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The protein expressions of COX2, ACSL4, PTGS2, GPX4, and NOX1 were analyzed by Western blot. Flow cytometry and TUNEL assays were used to assess cell reactive oxygen species (ROS) and ferroptosis, respectively. Cell invasion and migration were measured by Transwell assay. To evaluate the ferroptosis of M1-type macrophages, glutathione (GSH), malondialdehyde (MDA), and Fe2+ content was detected by corresponding kits. Dual luciferase reporter gene detection verified the targeting relationship between miR-142-3p and SLC3A2. Results: MiR-142-3p was highly expressed in HBV-infected HCC patients and HBV-infected M1-type macrophages. Inhibition of miR-142-3p or overexpression of SLC3A2 reversed ferroptosis and inhibited the proliferation, migration, and invasion of HCC cells. Conclusions: Our findings indicated that miR-142-3p promoted HBV-infected M1-type macrophage ferroptosis through SLC3A2, affecting the production of GSH, MDA, and Fe2+ and accelerating the development of HCC. The regulation of miR-142-3p and its target genes will help to clarify the pathogenesis of HCC induced by HBV infection and provide new theoretical foundations and therapeutic targets. 2022 Journal of Gastrointestinal Oncology. All rights reserved.
Entities:
Keywords:
MiR-142-3p; SLC3A2; hepatitis B virus (HBV); hepatocellular carcinoma (HCC)
Authors: Elizabeth M Kenny; Emin Fidan; Qin Yang; Tamil S Anthonymuthu; Lee Ann New; Elizabeth A Meyer; Hong Wang; Patrick M Kochanek; C Edward Dixon; Valerian E Kagan; Hülya Bayir Journal: Crit Care Med Date: 2019-03 Impact factor: 7.598
Authors: Nada Sonda; Francesca Simonato; Elisa Peranzoni; Bianca Calì; Stefania Bortoluzzi; Andrea Bisognin; Ena Wang; Francesco M Marincola; Luigi Naldini; Bernhard Gentner; Christian Trautwein; Sara Dutton Sackett; Paola Zanovello; Barbara Molon; Vincenzo Bronte Journal: Immunity Date: 2013-06-27 Impact factor: 31.745