C10ORF10

Official Full Name

DEPP autophagy regulator 1

Organism

Homo sapiens

GeneID

11067

Background

The expression of this gene is induced by fasting as well as by progesterone. The protein encoded by this gene contains a t-synaptosome-associated protein receptor (SNARE) coiled-coil homology domain and a peroxisomal targeting signal. Production of the encoded protein leads to phosphorylation and activation of the transcription factor ELK1. [provided by RefSeq, Jul 2008]

Synonyms

DEPP1; FIG; DEPP; Fseg; C10orf10;

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Detailed Information

Recent Research Progress

The C10orf10 gene was originally cloned from a human womb and was located at the position of q11.21 on human chromosome 10. The gene, which encodes 212 amino acids, has a cognate domain of convoluted T synaptic corpuscular protein receptors and a peroxisome localization signal. The gene is highly expressed in kidney, placenta, liver, ovary and other tissues. Studies have shown that progesterone, androgens and hypoxia conditions can induce the expression of C10orf10 gene. Overexpression of C10orf10 can activate the activity of the transcription factor Ets-like protein 1(Elk-1) and increase the expression level of phosphorylated mitogen-activated protein kinase (MAPK), and the expression of C10orf10 is directly regulated by the transcription of FOXO and FOXO3 proteins. Recent studies have confirmed that C10orf10 and its gene products play an important role in the occurrence and chemotherapy of related tumors.

Expression of C10orf10 gene in breast cancer (BC) and its relationship with clinicopathological characteristics

Several reports show that C10orf10 may be an important prognostic factor inBC,its expression is significantly related to theclinicopathological features of BC. Li et al. detected the expression of C10orf10 in 200 cases of BC and 121 cases of normal adjacent tissues. The results showed that the relative expression of C10orf10 in the tissues of BC patients was significantly lower than that of normal adjacent tissues, regardless of the mRNA level or protein level (Figure.1). Further analysis revealed that the expression of C10orf10 was related to Tumor Node Metastasis (TNM) stage, leibar junction metastasis and HER-2 expression. This suggests that C10orf10 plays an important role in the development of BC. Therefore, it is necessary to further study the cell biology of C10orf10 and its potential as a therapeutic target for BC.

Figure. 1 protein expression of C10orf10 in BC tissue and normal adjacent tissues(Li,Linhai, et al. 2016)

C10ORF10/DEPP, a transcriptional target of FOXO3, regulates ROS-sensitivity in human neuroblastoma.

DEPP, the human c10orf10 gene product, can regulate ROS detoxification and localizes to peroxisomes and mitochondria in neuroblastoma cells. FOXO3-mediated apoptosis involves a biphasic ROS accumulation. Knockdown of DEPP prevented the primary and secondary ROS wave during FOXO3 activation and attenuated FOXO3- and H2O2-induced apoptosis. Conditional overexpression of DEPP elevates cellular ROS levels and sensitizes to H2O2 and etoposide-induced cell death. In neuronal cells, cellular ROS are mainly detoxified in peroxisomes by the enzyme CAT/catalase. Furthermore, the FOXO3-regulated gene DEPP modulates the induction of autophagy in human neuroblastoma. Further research suggests that H2O2-treatment triggers autophagy-induction by FOXO3-mediated DEPP expression. Importantly, knockdown of DEPP was sufficient to efficiently inhibit autophagy-induction under different stress conditions such as serum starvation and genotoxic stress, suggesting that DEPP expression is critical for the initiation of autophagy in neuroblastoma. FOXO3-triggered autophagy partially protects neuroblastoma cells from cell death.

In addition, the study found that C10orf10 expression associated with hypoxia, hormone and ionizing radiation. It means that the C10orf10 expression and tumor radiation and chemotherapy may have correlation. However, the expression and clinical significance of C10orf10 in cancer remains unclear. Therefore, further study on the function of C10orf10 gene undoubtedly has important theoretical significance and potential application value of clinical diagnosis.

References:

Li,Linhai, et al. Expression of C10orf10 gene in breast cancer and its relationship with clinicopathologicalfeatures.Chinese Journal Of Breast Disease, 2016, 10(04):226-230.
Deng,Junjiang, et al. Decreased expression of C10orf10 and its prognostic significance in human breast cancer. PLoS One, 2014, 9( 6): e99730.
Salcher, et al. C10orf10 /DEPP, a transcriptional target of FOXO3, regulates ROS-sensitivity in human neuroblastoma. Mol Cancer, 2014, 13: 224.
Salcher, et al.C10ORF10/DEPP-mediated ROS accumulation is a critical modulator of FOXO3-induced autophagy. Molecular Cancer, 2017, 16:95.

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