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LncRNA DANCR promotes tumor growth and angiogenesis in ovarian cancer through direct targeting of miR‐145
Author(s) -
Lin Xiaojuan,
Yang Fan,
Qi Xiaorong,
Li Qingli,
Wang Danqing,
Yi Tao,
Yin Rutie,
Zhao Xia,
Zhong Xiaomin,
Bian Ce
Publication year - 2019
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.23117
Subject(s) - angiogenesis , biology , ovarian cancer , cancer research , gene knockdown , ovarian tumor , matrigel , cancer , vascular endothelial growth factor , tumor progression , cd31 , cell culture , genetics , vegf receptors
Differentiation antagonizing non‐protein coding RNA (DANCR) is a newly identified oncogenic long noncoding RNA found in various cancers. However, the functional role of DANCR in tumor angiogenesis and the underlying mechanisms are still unclear. The expression of DANCR was determined in ovarian malignant tissues and cell lines. The functional role of DANCR in tumor angiogenesis was revealed by the following methods: CD31 staining of ovarian tumor tissues, matrigel‐plug assay tissues, HUVEC‐related tube formation assay, and invasion assay. Enzyme‐linked immunosorbent assay, Western blotting, luciferase assay, and rescue experiments were used to investigate the underlying mechanisms of DANCR‐regulating angiogenesis. DANCR was upregulated in ovarian malignant tissues and ovarian cancer cells. Knockdown of DANCR efficiently impaired ovarian tumor growth through inhibition of tumor angiogenesis. Furthermore, the conditional culture medium from DANCR‐knockdown ovarian cells significantly inhibited tube formation and invasion of HUVEC in vitro. Mechanistic investigation indicated that vascular endothelial growth factor A (VEGF‐A, VEGF) plays a crucial role during DANCR inhibition of tumor angiogenesis in ovarian cancer. Further results demonstrated that miR‐145 is the direct binding target of DANCR during regulation of VEGF expression and tumor angiogenesis in ovarian cancer cells. Collectively, DANCR plays a promotional role in tumor angiogenesis in ovarian cancer through regulation of miR‐145/VEGF axis. Therefore, DANCR may be a novel therapy target for ovarian cancer.