期刊
LIFE SCIENCES
卷 264, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2020.118636
关键词
HOXB-AS3; miR-378a-3p; Glycolysis
资金
- National Natural Science Foundation of China [81872379, 81402139]
- Nanjing Medical Science and Technique Development Foundation [YKK17182, QRX17157, ZKX17042]
- Nanjing Technological Development Program [201715049]
- Science and technology development foundation item of Nanjing medical university [NMUB2017079]
The study demonstrates that HOXB-AS3 is abundantly expressed in epithelial ovarian cancer tissues and higher levels are associated with disease status and overall survival. Knockdown of HOXB-AS3 inhibits proliferation, invasion, and migration of EOC cells by decreasing LDHA expression and ECAR through sponging miR-378a-3p. This suggests HOXB-AS3 could be a predictor of OS and a potential 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.
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