| Title | Decreased ZNF750 promotes angiogenesis in a paracrine manner via activating DANCR/miR-4707-3p/FOXC2 axis in esophageal squamous cell carcinoma |
| Authors | Bi, Yanghui Guo, Shixing Xu, Xiaoqin Kong, Pengzhou Cui, Heyang Yan, Ting Ma, Yanchun Cheng, Yikun Chen, Yunqing Liu, Xue Zhang, Ling Cheng, Caixia Xu, Enwei Qian, Yu Yang, Jian Song, Bin Li, Hongyi Wang, Fang Hu, Xiaoling Liu, Xiangchen Niu, Xia Zhai, Yuanfang Liu, Jing Li, Yaoping Cheng, Xiaolong Cui, Yongping |
| Affiliation | Shanxi Med Univ, Dept Pathol, Taiyuan 030001, Shanxi, Peoples R China Shanxi Med Univ, Shanxi Key Lab Carcinogenesis & Translat Res Esop, Taiyuan 030001, Shanxi, Peoples R China Peking Univ, Shenzhen Hosp, Hong Kong Univ Sci & Technol PKU HKUST, Shenzhen Peking Univ,Med Ctr, Shenzhen 518035, Peoples R China Univ Calif Berkeley, Coll Letter & Sci, Berkeley, CA 94704 USA Shanxi Canc Hosp, Surg Special Wards, Taiyuan 030001, Shanxi, Peoples R China Shanxi Med Univ, Hosp 1, Dept Pathol, Taiyuan 030001, Shanxi, Peoples R China Shanxi Canc Hosp, Dept Pathol, Taiyuan 030001, Shanxi, Peoples R China Shanxi Med Univ, Hosp 1, Dept Oncol, Taiyuan 030001, Shanxi, Peoples R China Shanxi Med Univ, Hosp 1, Dept Gen Surg, Taiyuan 030001, Shanxi, Peoples R China Shanxi Med Univ, Affiliated Prov Hosp, Dept Colorectal & Anal Surg, Taiyuan 030001, Shanxi, Peoples R China |
| Keywords | TRANSCRIPTION FACTOR TUMOR PROGRESSION LNCRNA-DANCR CANCER METASTASIS GENES EXPRESSION KLF4 |
| Issue Date | 27-Apr-2020 |
| Publisher | CELL DEATH & DISEASE |
| Abstract | ZNF750 is one novel significantly mutated gene identified in esophageal squamous cell carcinoma (ESCC) using next-generation sequencing. However, its clinically relevant and potential mechanisms have remained elusive. Using genomic sequencing of 612 ESCC patients, we analyzed the associations of ZNF750 mutations with clinicopathologic features and its prognostic value. We further investigated the function and underlying mechanism of ZNF750 in angiogenesis. The results showed ZNF750 mutations/deletions are significantly associated with malignant progression and poor prognosis of ESCC patients. Decreased ZNF750 in ESCC cells induces enhanced angiogenesis of human umbilical vein endothelial cells (HUVECs) and human arterial endothelial cells (HAECs), and the effect may be indirectly mediated by FOXC2. RNA-seq and ChIP shows lncRNA DANCR is a direct downstream target of ZNF750. Furtherly, knockdown ZNF750 evokes DANCR expression, which prevents miR-4707-3p to interact with FOXC2 as a microRNA sponge in a ceRNA manner, leading to enhanced FOXC2 signaling and angiogenesis. In contrast, ZNF750 expression reverses the effect. Our study reveals a novel mechanism of ZNF750, highlights a significance of ZNF750 as a metastatic and prognostic biomarker, and offers potential therapeutic targets for ESCC patients harboring ZNF750 mutations. |
| URI | http://hdl.handle.net/20.500.11897/588701 |
| ISSN | 2041-4889 |
| DOI | 10.1038/s41419-020-2492-2 |
| Indexed | SCI(E) |
| Appears in Collections: | 深圳医院 |
