Comprehensive analysis of the HOXA gene family identifies HOXA13 as a novel oncogenic gene in kidney renal clear cell carcinoma.
Biomarkers, Tumor
/ biosynthesis
Carcinoma, Renal Cell
/ genetics
Cell Line, Tumor
Cell Proliferation
/ genetics
Cyclin D1
/ metabolism
Databases, Genetic
Down-Regulation
Gene Knockdown Techniques
Homeodomain Proteins
/ biosynthesis
Humans
Kidney Neoplasms
/ genetics
Multigene Family
Oncogenes
RNA, Messenger
/ genetics
Transcription Factors
/ biosynthesis
Transcription, Genetic
Tumor Suppressor Protein p53
/ metabolism
Up-Regulation
HOXA13
Homeobox-A cluster genes
Kidney renal clear cell carcinoma
Oncogene
Prognosis
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
15
01
2020
accepted:
13
05
2020
pubmed:
24
5
2020
medline:
14
7
2020
entrez:
24
5
2020
Statut:
ppublish
Résumé
Kidney renal clear cell carcinoma (KIRC) is one of the most common lethal cancers in the human urogenital system. As members of the Homeobox (HOX) family, Homeobox-A (HOXA) cluster genes have been reported to be involved in the development of many cancer types. However, the expression and clinical significance of HOXA genes in KIRC remain largely unknown. In this study, we comprehensively analyzed the mRNA expression and prognostic values of HOXA genes in KIRC using The Cancer Genome Atlas (TCGA) analysis databases online. Colony formation assay, flow cytometry and Western blot were used to detect cell proliferation, apoptosis, cell cycle, and protein level of the indicated gene. We found that the HOXA genes were differentially expressed in KIRC tissues when compared with normal tissues. The expression of HOXA4 and HOXA13 were significantly up-regulated, while HOXA7 and HOXA11 were down-regulated in KIRC. High mRNA levels of HOXA2, HOXA3 and HOXA13, and low level of HOXA7 predicted poor overall survival (OS) of KIRC patients. High mRNA level of HOXA13 further indicated a poor disease-free survival (DFS) of KIRC patients. Functionally, knockdown of HOXA13 significantly suppressed cell proliferation of KIRC in vitro, increased the protein level of p53 and decreased the protein level of cyclin D1 in KIRC cells. Over-expression of HOXA13 had the opposite effects on KIRC cells. Collectively, our findings suggest that HOXA13 functions as a novel oncogene in KIRC and may be a potential biomarker for this malignancy.
Identifiants
pubmed: 32444962
doi: 10.1007/s00432-020-03259-x
pii: 10.1007/s00432-020-03259-x
doi:
Substances chimiques
Biomarkers, Tumor
0
CCND1 protein, human
0
HOXA7 protein, human
0
Homeodomain Proteins
0
RNA, Messenger
0
TP53 protein, human
0
Transcription Factors
0
Tumor Suppressor Protein p53
0
homeobox protein HOXA13
0
HOXA4 protein, human
127609-92-1
Cyclin D1
136601-57-5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1993-2006Subventions
Organisme : the Key Scientific Research Projects of Institutions of Higher Learning in Henan Province
ID : 20A310018
Organisme : the Provincial Co-construction Project of Medical Science and Technology in Henan
ID : SB201903032
Organisme : the Key Scientific and Technological Project in Henan Province
ID : 182102310328
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