Sujuan Xu1, Genmei Jia2, Huilin Zhang3, Luyao Wang2, Yu Cong2, Mingming Lv2, Juan Xu2, Hongjie Ruan3, Xuemei Jia3, Pengfei Xu4, Yingwei Wang5. 1. Nanjing Maternity and Child Health Care Institute, Women's Hospital of Nanjing medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 210004, China; Department of Immunology, Nanjing Medical University, Nanjing, China; Department of Clinical Laboratory, Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 210004, China. 2. Nanjing Maternity and Child Health Care Institute, Women's Hospital of Nanjing medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 210004, China. 3. Department of Gynecology, Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 210004, China. 4. Nanjing Maternity and Child Health Care Institute, Women's Hospital of Nanjing medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 210004, China. Electronic address: pengfeixu@njmu.edu.cn. 5. Department of Immunology, Nanjing Medical University, Nanjing, China. Electronic address: wangyw1508@njmu.edu.cn.
Abstract
HEADING AIMS: LncRNA HOXB-AS3 is proved as an oncogene in tumors. Herein, we determine the function and mechanism of HOXB-AS3 in epithelial ovarian cancer (EOC) cells. MATERIALS AND METHODS: Chi-square test, Kaplan-Meier (KM) analysis and Cox regression analysis were used to analyze the clinicopathological features of HOXB-AS3 in EOC patients. CCK8, transwell and wound healing assay were used to test the function of HOXB-AS3. Luciferase reporter assay, western blot and glycolysis rate assay were used for further mechanistic studies. KEY FINDINGS: HOXB-AS3 was abundantly expressed in EOC tissues, and higher levels of HOXB-AS3 in EOC patients were significantly associated with disease status and overall survival status. EOC patients with high levels of HOXB-AS3 had strikingly shorter disease-free survival (DFS) and overall survival (OS) times than those with low levels. HOXB-AS3 also might as an independent prognostic factor. Further study revealed knockdown of HOXB-AS3 significantly inhibited the proliferation, invasion and migration of EOC cells. Mechanistic investigations suggested that knockdown of HOXB-AS3 could decrease lactate dehydrogenase A (LDHA) expression and the extracellular acidification rate (ECAR) by sponging miR-378a-3p. SIGNIFICANCE: To our knowledge, this is the first study to suggest that HOXB-AS3 could crosstalk with miRNA in the cytoplasm and alter glycolysis in cancer cells. Our results improve our understanding of the mechanism of HOXB-AS3 and suggest that HOXB-AS3 can act as a predictor of OS and a target for EOC therapies.
HEADING AIMS: LncRNA HOXB-AS3 is proved as an oncogene in tumors. Herein, we determine the function and mechanism of HOXB-AS3 in epithelial ovarian cancer (EOC) cells. MATERIALS AND METHODS: Chi-square test, Kaplan-Meier (KM) analysis and Cox regression analysis were used to analyze the clinicopathological features of HOXB-AS3 in EOC patients. CCK8, transwell and wound healing assay were used to test the function of HOXB-AS3. Luciferase reporter assay, western blot and glycolysis rate assay were used for further mechanistic studies. KEY FINDINGS: HOXB-AS3 was abundantly expressed in EOC tissues, and higher levels of HOXB-AS3 in EOC patients were significantly associated with disease status and overall survival status. EOC patients with high levels of HOXB-AS3 had strikingly shorter disease-free survival (DFS) and overall survival (OS) times than those with low levels. HOXB-AS3 also might as an independent prognostic factor. Further study revealed knockdown of HOXB-AS3 significantly inhibited the proliferation, invasion and migration of EOC cells. Mechanistic investigations suggested that knockdown of HOXB-AS3 could decrease lactate dehydrogenase A (LDHA) expression and the extracellular acidification rate (ECAR) by sponging miR-378a-3p. SIGNIFICANCE: To our knowledge, this is the first study to suggest that HOXB-AS3 could crosstalk with miRNA in the cytoplasm and alter glycolysis in cancer cells. Our results improve our understanding of the mechanism of HOXB-AS3 and suggest that HOXB-AS3 can act as a predictor of OS and a target for EOC therapies.