Research Paper Volume 12, Issue 19 pp 19375—19398
HOXC10 promotes tumour metastasis by regulating the EMT-related gene Slug in ovarian cancer
- 1 Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China
- 2 School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China
- 3 Department of Gynecology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China
Received: February 27, 2020 Accepted: July 14, 2020 Published: September 7, 2020
https://doi.org/10.18632/aging.103824How to Cite
Copyright: © 2020 Peng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The mortality rate of ovarian cancer is the highest among gynaecological cancers, primarily due to metastatic symptoms. Recent studies have shown that HOX genes are crucial in tumour progression, but the underlying mechanisms remain unclear. Here, HOXC10 expression was examined in ovarian cancer tissues. The function of HOXC10 in ovarian cancer metastasis was investigated in vitroand via intraperitoneal injection in vivo. A total of 158 ovarian cancer patients with adequate records were enrolled for analysis. HOXC10 was associated with metastasis and poor prognosis in ovarian cancer. In vitro, HOXC10 overexpression promoted ovarian cancer cell migration. Moreover, HOXC10 positively regulated Slug expression, altering the migration ability of cancer cells. Furthermore, our study showed that miR-222-3p was a suppressor of HOXC10. In vivo, a decrease in hepatic metastasis was seen in xenograft mice harbouring tumours with stable HOXC10 overexpression after miR-222-3p agomir (an overexpression reagent) injection. This study provides the first evidence that HOXC10 promotes ovarian cancer metastasis by regulating the transcription of the EMT-related gene Slug. Moreover, we found that HOXC10 is regulated by miR-222-3p. These data highlight the crucial role of HOXC10 in enhancing ovarian cancer metastasis and may provide a therapeutic target for ovarian cancer.
Abbreviations
HOX: homeobox; EMT: epithelial-mesenchymal transition; miRNA: microRNA; IL-6: interleukin-6; IHC: immunohistochemistry; CHIP: chromatin immunoprecipitation assay; NLS: nuclear localization signal; OC: ovarian cancer; EGF: epidermal growth factor; STAT4: signal transducer and activator of transcription 4; HDAC: histone deacetylase; TCF4: transcription factor 4; KLF4: kruppel-like factors 4; GPC3: glypican-3; DMEM: dulbecco’s modified eagle’s medium; FBS: fetal bovine serum; FIGO: the International Federation of Gynecology and Obstetrics; TCGA: the cancer genome atlas; GSEA: gene-set enrichment analysis; 3’-UTR: three prime untranslated region; DAPI: 4′,6-diamidino-2-phenylindole; GNAI2: guanine nucleotide-binding protein G(i) subunit alpha-2.