Zhen He1. 1. Department of Gastroenterology, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Abstract
Background: Esophageal squamous cell carcinoma (ESCC) is one of the esophageal cancers known as an aggressive malignant tumor. Long noncoding RNAs (lncRNAs) can be involved in the progression and development of cancers. lncRNA LINC00473 (LINC00473) was reported to exert an oncogenic influence on diverse cancers. However, neither the biological function nor the underlying mechanism of LINC00473 has been explored in ESCC. Aim of the Study: The aim of investigation is to explore the role of LINC00473 in ESCC. Methods: The expression of LINC00473, miR-497-5p, and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) was detected by reverse-transcription quantitative polymerase chain reaction assay. Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were carried out to measure cell proliferation. Cell migration was tested by transwell assay. Western blot assay was performed to examine the protein expression of PRKAA1, E-cadherin, N-cadherin, and Vimentin. The binding capacity between miR-497-5p and LINC00473 (or PRKAA1) was, respectively, studied by luciferase reporter and RNA immunoprecipitation assays. Pearson correlation analysis was adopted to analyze the correlation between miR-497-5p (or LINC00473) and PRKAA1. Results: LINC00473 presented much higher expression and LINC00473 suppression restrained the proliferation, migration, and epithelial-mesenchymal transition (EMT) process in ESCC cells. MiR-497-5p presented lower expression, binding with and negatively regulated by LINC00473 in ESCC. PRKAA1 was confirmed as a downstream target gene for miR-497-5p. PRKAA1 could combine with miR-497-5p, and LINC00473 knockdown or miR-497-5p overexpression downregulated the mRNA and protein expression of PRKAA1. At last, the inhibitory effects of LINC00473 knockdown on proliferation, migration, and EMT process were reversed by PRKAA1 overexpression in vitro and in vivo. Conclusions: LINC00473 regulates ESCC progression through miR-497-5p/PRKAA1 axis, which provides a new therapeutic strategy for ESCC patients.
Background: Esophageal squamous cell carcinoma (ESCC) is one of the esophageal cancers known as an aggressive malignant tumor. Long noncoding RNAs (lncRNAs) can be involved in the progression and development of cancers. lncRNA LINC00473 (LINC00473) was reported to exert an oncogenic influence on diverse cancers. However, neither the biological function nor the underlying mechanism of LINC00473 has been explored in ESCC. Aim of the Study: The aim of investigation is to explore the role of LINC00473 in ESCC. Methods: The expression of LINC00473, miR-497-5p, and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) was detected by reverse-transcription quantitative polymerase chain reaction assay. Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were carried out to measure cell proliferation. Cell migration was tested by transwell assay. Western blot assay was performed to examine the protein expression of PRKAA1, E-cadherin, N-cadherin, and Vimentin. The binding capacity between miR-497-5p and LINC00473 (or PRKAA1) was, respectively, studied by luciferase reporter and RNA immunoprecipitation assays. Pearson correlation analysis was adopted to analyze the correlation between miR-497-5p (or LINC00473) and PRKAA1. Results:LINC00473 presented much higher expression and LINC00473 suppression restrained the proliferation, migration, and epithelial-mesenchymal transition (EMT) process in ESCC cells. MiR-497-5p presented lower expression, binding with and negatively regulated by LINC00473 in ESCC. PRKAA1 was confirmed as a downstream target gene for miR-497-5p. PRKAA1 could combine with miR-497-5p, and LINC00473 knockdown or miR-497-5p overexpression downregulated the mRNA and protein expression of PRKAA1. At last, the inhibitory effects of LINC00473 knockdown on proliferation, migration, and EMT process were reversed by PRKAA1 overexpression in vitro and in vivo. Conclusions: LINC00473 regulates ESCC progression through miR-497-5p/PRKAA1 axis, which provides a new therapeutic strategy for ESCCpatients.