ORIGINAL ARTICLE   

Panminerva Medica 2022 December;64(4):532-6

DOI: 10.23736/S0031-0808.20.03911-7

Copyright © 2020 EDIZIONI MINERVA MEDICA

language: English

HOXD9 aggravates the development of cervical cancer by transcriptionally activating HMCN1

Dan WEN ¹ ✉, Li WANG ², Songhong TAN ³, Rong TANG ⁴, Weimin XIE ³, Shanyan LIU ¹, Caixia TANG ¹, Yingxin HE ¹

¹ Department of Gynecology and Obstetrics, Affiliated Nanhua Hospital, University of South China, Hengyang, China; ² Department of Gynecology and Obstetrics, Tongren Municipal People’s Hospital, Tongren, China; ³ Department of Gynecology and Obstetrics, Affiliated Hengyang Hospital, Southern Medical University (Hengyang Central Hospital), Hengyang, China; ⁴ Department of Gastrointestinal Surgery, The First Affiliated Hospital of University of South China, Hengyang, China

BACKGROUND: To detect HOXD9 levels in cervical cancer species and to explore the relationship between HOXD9 level and prognosis in cervical cancer patients. We also verify the influence of HOXD9 on metastatic abilities in cervical cancer.
METHODS: HOXD9 levels in cervical cancer species were detected. Its influence on clinical features and prognosis in cervical cancer patients was analyzed. Regulatory effects of HOXD9 on migratory and invasive capacities in C33-A and HeLa cells were evaluated by Transwell assay. Subsequently, the downstream gene of HOXD9 was predicted by bioinformatics analysis and confirmed by luciferase assay. The involvement of HMCN1 in regulating metastatic ability in cervical cancer cells was finally explored by rescue experiments.
RESULTS: HOXD9 was upregulated in cervical cancer species and its level was positively correlated to rates of lymphatic metastasis and distant metastasis. High level of HOXD9 in cervical cancer patients predicted a poor prognosis. Overexpression of HOXD9 promoted migratory and invasive capacities in cervical cancer cells. HMCN1 was identified to be the downstream gene binding HOXD9. It was responsible for HOXD9-regulated metastasis in cervical cancer.
CONCLUSIONS: HOXD9 is upregulated in cervical cancer species. Its level is closely linked to metastasis rate and poor prognosis in cervical cancer patients. Through positively regulating HMCN1 level, HOXD9 stimulates migratory and invasive capacities in cervical cancer cells.

KEY WORDS: HOXD9 protein, human; HMCN1 protein, human; Uterine cervical neoplasms; Neoplasm metastasis