Zhigang Liu1,2, Yun Lü3, Qiuyu Jiang4, Yang Yang5, Chengxue Dang1, Ruifang Sun6. 1. Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China. 2. Department of Thoracic Surgery, Shaanxi Provincial Tumor Hospital, Xi'an Jiaotong University, Xi'an, P.R. China. 3. Pharmacy Intravenous Admixture Services, Shaanxi Provincial Tumor Hospital, Xi'an Jiaotong University, Xi'an, P.R. China. 4. Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, P.R. China. 5. School of Public Health, Xi'an Jiaotong University, Xi'an, P.R. China. 6. Department of Pathology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
Abstract
PURPOSE: miR-491 functions as a tumor suppressor in several types of cancer. However, its function and mechanism in gastric cancer proliferation and metastasis have not been well defined. The aim of this study was to explore the role and regulatory mechanism of miR-491 in cell proliferation and migration in gastric cancer. METHODS: Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the expression pattern of miR-491 in gastric cancer tissues. miR-491 overexpression vector, miR-491 inhibitor, and siHMGA2 were used; and MTT, wound healing, and transwell assays were employed to examine proliferation and migration for BGC-823 cells. A dual-luciferase reporter gene was used to measure the target relationship between miR-491 and HMGA2. RESULTS: Most gastric cancer patients exhibit decreased miR-491 expression. miR-491 overexpression inhibited cell proliferation and migration, whereas miR-491 inhibitor treatment produced the opposite effect. Mechanistically, HMGA2 was identified as a direct target of miR-491. Moreover, HMGA2 knockdown inhibited cell proliferation and migration, which was similar to the effect of miR-491 overexpression. HMGA2 was decreased after transfection of the miR-491 vector and increased after transfection of the miR-491 inhibitor. CONCLUSION: Our results suggest that miR-491 suppressed cell proliferation and cell motility in gastric cancer by targeting HMGA2. Silencing HMGA2 produced a similar effect to miR-491 overexpression on cell proliferation and migration. miR-491/HMGA2 signaling may be a potential therapeutic target for gastric cancer patients with decreased miR-491 expression.
PURPOSE: miR-491 functions as a tumor suppressor in several types of cancer. However, its function and mechanism in gastric cancer proliferation and metastasis have not been well defined. The aim of this study was to explore the role and regulatory mechanism of miR-491 in cell proliferation and migration in gastric cancer. METHODS: Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the expression pattern of miR-491 in gastric cancer tissues. miR-491 overexpression vector, miR-491 inhibitor, and siHMGA2 were used; and MTT, wound healing, and transwell assays were employed to examine proliferation and migration for BGC-823 cells. A dual-luciferase reporter gene was used to measure the target relationship between miR-491 and HMGA2. RESULTS: Most gastric cancer patients exhibit decreased miR-491 expression. miR-491 overexpression inhibited cell proliferation and migration, whereas miR-491 inhibitor treatment produced the opposite effect. Mechanistically, HMGA2 was identified as a direct target of miR-491. Moreover, HMGA2 knockdown inhibited cell proliferation and migration, which was similar to the effect of miR-491 overexpression. HMGA2 was decreased after transfection of the miR-491 vector and increased after transfection of the miR-491 inhibitor. CONCLUSION: Our results suggest that miR-491 suppressed cell proliferation and cell motility in gastric cancer by targeting HMGA2. Silencing HMGA2 produced a similar effect to miR-491 overexpression on cell proliferation and migration. miR-491/HMGA2 signaling may be a potential therapeutic target for gastric cancer patients with decreased miR-491 expression.
Authors: Behzad Mansoori; Ali Mohammadi; Henrik J Ditzel; Pascal H G Duijf; Vahid Khaze; Morten F Gjerstorff; Behzad Baradaran Journal: Genes (Basel) Date: 2021-02-13 Impact factor: 4.096