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C2orf40

Official Full Name
Homo sapiens chromosome 2 open reading frame 40 DNA.
Synonyms
C2ORF40; chromosome 2 open reading frame 40; augurin; ECRG4; esophageal cancer related gene 4 protein; esophageal cancer-related gene 4 protein

Recent Research Progress

The esophageal cancer-associated gene 4 (ECRG4), also known as C2orf40, is located on chromosome 2q12.2. ECRG4 is a tumor suppressor gene that was originally identified and cloned from human esophageal epithelial cells in 1998. ECRG4 is widely expressed in normal human tissues. It has been reported that ECRG4 is expressed at low or undetectable levels in various malignant tumor tissues and cell lines, and the expression level of ECRG4 is closely related to tumor proliferation and apoptosis.

ECRG4 and renal cancer

Recent studies indicated that expression of ECRG4 was down-regulated in renal cell lines and renal cancer tissues. ECRG4 expression was significantly associated with histological grade of the tumor, primary tumor stage and distant metastasis. Low expression of ECRG4 is an independent prognostic indicator for survival in patients with renal cancer. Silencing of ECRG4 expression in renal cell lines is associated with promoter methylation. Furthermore, ectopic expression of ECRG4 significantly inhibited cell proliferation and invasion in renal cancer cell lines. These results indicate that ECRG4 is often silenced by methylation of the promoter in renal cell carcinoma. ECRG4 can be a tumor suppressor in kidney cancer and is used as a prognostic marker.

ECRG4 and Laryngeal cancer

Laryngeal cancer is a malignant tumor that originates in the epithelial tissue of the laryngeal mucosa. Recently, the study found that ECRG4 inhibited the growth of laryngeal cancer cells through arresting cells in the G0 / G1 phase and delaying cell cycle from G0 / G1 phase to S phase and G2 / M phase. In addition, overexpression of ECRG4 activated caspase-3 and poly ADP-ribose polymerase (PARP), and ultimately induces apoptosis by up-regulating the expression of the pro-apoptotic protein Bax and down-regulating the expression of the anti-apoptotic protein Bcl-2. Hence, overexpression of ECRG4 may become an effective gene therapy strategy for the treatment of laryngeal cancer.

ECRG4 and NPC

Human nasopharyngeal carcinoma (NPC) is a malignant type of cancer with an increasing incidence. However, to date, molecular biomarkers with powerful diagnostic impacts and major therapeutic prospects have remained elusive. Recently, studies have found that expression of ECRG4 was noted in primary NPC tumors relative to normal tissues, and this decreased expression was found to be associated with its promoter methylation status. Yanjie You et al. found that ECRG4 promoter hypermethylation occurred frequently in primary NPC specimens, and its concomitant detection in peripheral blood samples showed high sensitivity and specificity for cancer diagnosis and monitoring.

ECRG4 and BC

The poor prognosis of breast cancer (BC) is largely due to early and frequent metastasis. So far, the mechanism of BC metastasis is unclear, and the appropriate molecular markers for BC metastasis and progression remain elusive. ECRG4 protein expression was significantly reduced in BC tissues compared to non-cancerous tissues. Recent studies have shown that lack of ECRG4 protein expression may lead to metastatic potential and progression of BC. In addition, ECRG4 protein expression has a significant impact on patient survival and, therefore, can serve as an independent prognostic factor.

ECRG4 and ESCC        

Esophageal squamous cell carcinoma (ESCC) is a highly invasive and clinically challenging cancer. Despite advances in clinically integrated therapy, the prognosis of ESCC remains poor due to its diffuse and aggressive nature. ECRG4 is a candidate tumor suppressor gene and is an independent prognostic factor of ESCC. Overexpression of ECRG4 gene inhibits proliferation and invasion of tumor cells in ESCC.

Taken together, studies have shown that ECRG4 can effectively inhibit the proliferation of tumor cells and induce apoptosis. In addition, there are data showing that ECRG4 may not only contribute to prognosis prediction, but may also provide new tailored treatment options. Consequently, further research on ECRG4 is undoubtedly necessary and valuable.

References:

  1. Linwei Li, et al. UBE2C is involved in the functions of ECRG4 on esophageal squamous cell carcinoma. Biomedicine & Pharmacotherapy, 2018, 98 : 201–206.
  2. Wang WY, et al. Beclin 1 promotes apoptosis and decreases invasion by upregulating the expression of ECRG4 in A549 human lung adenocarcinoma cells.Molecular Medicine Reports, 2016, 14(1): 355-360.
  3. Jia JP, et al. A preliminary study of the effect of ECRG4 overexpression on the proliferation and apoptosis of human laryngeal cancer cells and the underlying mechanisms. Molecular Medicine Reports, 2015, 12(4): 5058-5064.
  4. Yanjie You, et al. ECRG4 acts as a tumor suppressor and as a determinant of chemotherapy resistance in human nasopharyngeal carcinoma. Cell Oncol, 2015, 38:205–214.
  5. Jin Wang, et al. UBR5 Contributes to Colorectal Cancer Progression by Destabilizing the Tumor Suppressor ECRG4. Digestive Diseases And Sciences, 2017, 62(10): 2781-2789.
  6. Li XY, et al. Soluble purified recombinant C2ORF40 protein inhibits esophageal cancer cell proliferation by inducing cell cycle G1 phase block.Oncology Letters, 2015, 10(3): 1593-1596.
  7. Li LW, et al. Soluble purified recombinant C2ORF40 protein inhibits tumor cell growth in vivo by decreasing telomerase activity in esophageal squamous cell carcinoma. Oncology Letters, 2016, 12(4): 2820-2824.
  8. Chaoyang Li, et al. A short synthetic peptide fragment of human C2ORF40 has therapeutic potential in breast cancer. Oncotarget, 2017, 8(26): 41963-41974.
  9. Yanjie You, et al. Down-regulated ECRG4 expression in breast cancer and its correlation with tumor progression and poor prognosis - A short Report. Cell Oncol, 2016, 39:89–95.
  10. J.-Y. Chen, et al. Down-regulated ECRG4 is correlated with lymph node metastasis and predicts poor outcome for nasopharyngeal carcinoma patients. Clin Transl Oncol, 2017, 19:84–90.

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