HGNC Approved Gene Symbol: HOXC10
Cytogenetic location: 12q13.13 Genomic coordinates (GRCh38): 12:53,985,146-53,990,279 (from NCBI)
In a review of homeobox gene nomenclature, Scott (1992) listed HOXC10 as a member of the Hox C cluster on human chromosome 12. The HOXC10 sequence was entered into GenBank (XM006806 and NM017409). HOXC10 is homologous to mouse Hoxc10, which was previously called Hox3.6.
Zhai et al. (2007) found that HOXC10 was 1 of 171 genes upregulated at least 1.5-fold in invasive cervical squamous cell carcinomas compared with squamous intraepithelial lesions and normal cervix samples. Elevated HOXC10 expression was associated with increased invasiveness of human papillomavirus-immortalized keratinocytes and cervical cancer-derived cell lines in vitro and in vivo. Knockdown of HOXC10 expression with short hairpin RNA reduced cell invasiveness.
Pathiraja et al. (2014) identified widespread DNA hyper- and hypomethylation, with enrichment for promoter hypermethylation of developmental genes in 2 breast cancer cell line models of aromatase inhibitor resistance. For the homeobox gene HOXC10, methylation occurred in a CpG shore, which overlapped with a functional estrogen receptor (ER; 133430) binding site, causing repression of HOXC10 expression. Although short-term blockade of ER signaling caused relief of HOXC10 repression in both cell lines and breast tumors, it also resulted in concurrent recruitment of EZH2 (601573) and increased histone-3 lys27 trimethylation (H3K27me3; see 602810) ultimately transitioning to increased DNA methylation and silencing of HOXC10. Reduced HOXC10 in vitro and in xenografts resulted in decreased apoptosis and caused antiestrogen resistance. Supporting this, Pathiraja et al. (2014) used paired primary and metastatic breast cancer specimens to show that HOXC10 was reduced in tumors that recurred during aromatase inhibitor treatment. The authors proposed a model in which estrogen represses apoptotic and growth-inhibitory genes such as HOXC10, contributing to tumor survival; whereas aromatase inhibitors induce these genes to cause apoptosis and confer therapeutic benefit, long-term aromatase inhibitor treatment results in permanent repression of these genes via methylation and confers resistance. Pathiraja et al. (2014) suggested that therapies aimed at inhibiting aromatase inhibitor-induced histone and DNA methylation may be beneficial in blocking or delaying aromatase inhibitor resistance.
By database analysis, Priyanka et al. (2021) showed that the long noncoding RNA (lncRNA) HMS (LINC02381; 620723) was upregulated in many cancer types, including lung cancer. Knockdown of HMS resulted in cell cycle arrest at G1 phase and reduced migration and invasiveness of cancer cells. In contrast, HMS overexpression enhanced proliferation, mutation, and invasiveness of cancer cells. Depletion of HMS resulted in decreased expression of HOXC10. The RNA-binding protein HuR (ELAVL1; 603466) mediated stability of the HOXC10 transcript via the HOXC10 3-prime UTR. HuR interacted specifically with the cytosine-rich stretches of HMS, which recruited HuR to the 3-prime UTR of HOXC10, thereby facilitating HOXC10 mRNA stabilization. Database analysis revealed a positive correlation between HOXC10 and HMS expression in human cancer, suggesting that HMS functioning as a HOXC10 mRNA-stabilizing factor might play an essential role in cancer.
Scott (1992) stated that the HOXC10 gene belongs to the Hox C cluster on human chromosome 12 and mouse chromosome 15.
Priyanka et al. (2021) stated that the HOXC10 gene maps to chromosome 12q13.13.
Pathiraja, T. N., Nayak, S. R., Xi, Y., Jiang, S., Garee, J. P., Edwards, D. P., Lee, A. V., Chen, J., Shea, M. J., Santen, R. J., Gannon, F., Kangaspeska, S., and 10 others. Epigenetic reprogramming of HOXC10 in endocrine-resistant breast cancer. Sci. Transl. Med. 6: 229ra41, 2014. Note: Electronic Article. [PubMed: 24670685] [Full Text: https://doi.org/10.1126/scitranslmed.3008326]
Priyanka, P., Sharma, M., Das, S., Saxena, S. The lncRNA HMS recruits RNA-binding protein HuR to stabilize the 3-prime-UTR of HOXC10 mRNA. J. Biol. Chem. 297: 100997, 2021. [PubMed: 34302808] [Full Text: https://doi.org/10.1016/j.jbc.2021.100997]
Scott, M. P. Vertebrate homeobox gene nomenclature. Cell 71: 551-553, 1992. [PubMed: 1358459] [Full Text: https://doi.org/10.1016/0092-8674(92)90588-4]
Zhai, Y., Kuick, R., Nan, B., Ota, I., Weiss, S. J., Trimble, C. L., Fearon, E. R., Cho, K. R. Gene expression analysis of preinvasive and invasive cervical squamous cell carcinomas identifies HOXC10 as a key mediator of invasion. Cancer Res. 67: 10163-10172, 2007. [PubMed: 17974957] [Full Text: https://doi.org/10.1158/0008-5472.CAN-07-2056]