MicroRNA-370 Regulates Cellepithelial-Mesenchymal Transition, Migration, Invasion, and Prognosis of Hepatocellular Carcinoma by Targeting GUCD1
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Purpose: Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor, the prognosis of which remains poor. Recently,microRNAs have been reported to play crucial functions in multiple tumors, including HCC. However, the molecular mechanismsof miR-370 in HCC still remain largely unknown. The present study focused on the effects of miR-370 on HCC migration,invasion, and epithelial-mesenchymal transition (EMT). Materials and Methods: We investigated the key roles and possible regulatory mechanism of miR-370 in regulating HCC metastasiswith functional assays, such as transwell assay. Quantitative real-time PCR (qRT-PCR) was used to detect miR-370 and guanylylcyclasedomain containing 1 (GUCD1) expression in HCC tissues and cells. Subsequently, we performed transwell assays todetermine the functions of miR-370 in HCC cell invasion and migration. Western blot was used to determine protein expressionsof relevant genes. Luciferase reporter assays were conducted to confirm the target gene of miR-370. Results: qRT-PCR analysis demonstrated that miR-370 was dramatically downregulated in HCC. Moreover, downregulated miR-370 was found to be associated with poor survival and adverse clinicopathologic characteristics of HCC patients. Transwell assaysrevealed that miR-370 overexpression dramatically suppressed HCC invasion and migration. Meanwhile, miR-370 restorationprominently inhibited EMT progression in HCC cells. Luciferase reporter assays confirmed GUCD1 as a downstream target geneof miR-370. GUCD1 expression in HCC tissues was prominently increased and inversely correlated with miR-370 expression. Furthermore,GUCD1 was verified as mediating the suppressive influence of miR-370 on cell metastasis and EMT in HCC. Conclusion: Taken together, our study confirmed that miR-370 suppressed HCC cell metastasis and EMT via regulating GUCD1. Accordingly,the miR-370/GUCD1 axis may potentially acts as attractive therapeutic targets and novel biomarkers for HCC treatment.
Abstract
Purpose: Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor, the prognosis of which remains poor. Recently,microRNAs have been reported to play crucial functions in multiple tumors, including HCC. However, the molecular mechanismsof miR-370 in HCC still remain largely unknown. The present study focused on the effects of miR-370 on HCC migration,invasion, and epithelial-mesenchymal transition (EMT). Materials and Methods: We investigated the key roles and possible regulatory mechanism of miR-370 in regulating HCC metastasiswith functional assays, such as transwell assay. Quantitative real-time PCR (qRT-PCR) was used to detect miR-370 and guanylylcyclasedomain containing 1 (GUCD1) expression in HCC tissues and cells. Subsequently, we performed transwell assays todetermine the functions of miR-370 in HCC cell invasion and migration. Western blot was used to determine protein expressionsof relevant genes. Luciferase reporter assays were conducted to confirm the target gene of miR-370. Results: qRT-PCR analysis demonstrated that miR-370 was dramatically downregulated in HCC. Moreover, downregulated miR-370 was found to be associated with poor survival and adverse clinicopathologic characteristics of HCC patients. Transwell assaysrevealed that miR-370 overexpression dramatically suppressed HCC invasion and migration. Meanwhile, miR-370 restorationprominently inhibited EMT progression in HCC cells. Luciferase reporter assays confirmed GUCD1 as a downstream target geneof miR-370. GUCD1 expression in HCC tissues was prominently increased and inversely correlated with miR-370 expression. Furthermore,GUCD1 was verified as mediating the suppressive influence of miR-370 on cell metastasis and EMT in HCC. Conclusion: Taken together, our study confirmed that miR-370 suppressed HCC cell metastasis and EMT via regulating GUCD1. Accordingly,the miR-370/GUCD1 axis may potentially acts as attractive therapeutic targets and novel biomarkers for HCC treatment.
참고문헌 (31)
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