Heyuan Wang1,2, Guixia Wang1, Yufei Gao3, Conghai Zhao3, Xiaoping Li4, Fuqiang Zhang5, Chunyan Jiang6, Bing Wu3,7. 1. Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China. 2. Department of Immunology in College of Basic Medical Sciences, Jilin University, Changchun, China. 3. Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, China. 4. Department of Pediatric Endocrinology, The First Hospital of Jilin University, Changchun, China. 5. Science and Research Center, China-Japan Union Hospital of Jilin University, Changchun, China. 6. Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China. 7. Key Laboratory of Radiobiology (Ministry of Health) of Public Health, Jilin University, Changchun, China.
Abstract
BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) are critical regulators in various diseases including human cancer and could function as competing endogenous RNAs (ceRNAs) to regulate microRNAs (miRNAs). METHODS: Quantitative real-time PCR (qRT-PCR) was used to analyze the expression of lnc-SNHG1 and miR-302/372/373/520 in pituitary tumor tissues and cell lines. Cell proliferation was investigated using MTT and cell count assays. The mechanisms by which lnc-SNHG1 affects pituitary tumor progression were investigated using Western blot assays, transwell migration assays, immunohistochemistry, immunofluorescence, luciferase reporter assays, tumor xenografts, and flow cytometry Results: We found that lnc-SNHG1 was overexpressed in invasive pituitary tumor tissues and cell lines. Ectopic expression of lnc-SNHG1 promoted cell proliferation, migration, and invasion, as well as the epithelial-mesenchymal transition (EMT), by affecting the cell cycle and cell apoptosis in vitro and tumor growth in vivo. Further study indicated that overexpression of lnc-SNHG1 markedly inhibited the expression of miR-302/372/373/520 (miRNA-pool) which is down-regulated in invasive pituitary tumor cells. Moreover, overexpression of lnc-SNHG1 significantly promoted the expression of TGFBR2 and RAB11A, the direct targets of miR-302/372/373/520. Finally, lnc-SNHG1 activates the TGFBR2/SMAD3 and RAB11A/Wnt/β-catenin pathways in pituitary tumor cells via sponging miR-302/372/373/520. CONCLUSIONS: Our data suggest that lnc-SNHG1 promotes the progression of pituitary tumors and is a potential therapeutic target for invasive pituitary tumor.
BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) are critical regulators in various diseases including human cancer and could function as competing endogenous RNAs (ceRNAs) to regulate microRNAs (miRNAs). METHODS: Quantitative real-time PCR (qRT-PCR) was used to analyze the expression of lnc-SNHG1 and miR-302/372/373/520 in pituitary tumor tissues and cell lines. Cell proliferation was investigated using MTT and cell count assays. The mechanisms by which lnc-SNHG1 affects pituitary tumor progression were investigated using Western blot assays, transwell migration assays, immunohistochemistry, immunofluorescence, luciferase reporter assays, tumor xenografts, and flow cytometry Results: We found that lnc-SNHG1 was overexpressed in invasive pituitary tumor tissues and cell lines. Ectopic expression of lnc-SNHG1 promoted cell proliferation, migration, and invasion, as well as the epithelial-mesenchymal transition (EMT), by affecting the cell cycle and cell apoptosis in vitro and tumor growth in vivo. Further study indicated that overexpression of lnc-SNHG1 markedly inhibited the expression of miR-302/372/373/520 (miRNA-pool) which is down-regulated in invasive pituitary tumor cells. Moreover, overexpression of lnc-SNHG1 significantly promoted the expression of TGFBR2 and RAB11A, the direct targets of miR-302/372/373/520. Finally, lnc-SNHG1 activates the TGFBR2/SMAD3 and RAB11A/Wnt/β-catenin pathways in pituitary tumor cells via sponging miR-302/372/373/520. CONCLUSIONS: Our data suggest that lnc-SNHG1 promotes the progression of pituitary tumors and is a potential therapeutic target for invasive pituitary tumor.