Reciprocal regulation of BMF and BIRC5 (Survivin) linked to Eomes overexpression in colorectal cancer

Abstract

Eomesodermin (Eomes) is a T-box transcription factor that has been implicated in the etiology of colorectal cancer and other human malignancies. We screened a panel of human primary colon cancers and patient-matched controls (n = 30) and detected Eomes overexpression at the mRNA and protein level. Similar results were obtained in a panel of rat colon tumors and adjacent normal-looking colonic mucosa (n = 24). In human colon cancer cells, forced overexpression of Eomes enhanced cell viability and protected against staurosporine-induced apoptosis. On the other hand, knocking down Eomes resulted in reduced cell viability, G2/M cell cycle arrest, and apoptosis induction. The apoptotic mechanism centered on the reciprocal downregulation of anti-apoptotic BIRC5 (Survivin) and upregulation of proapoptotic Bcl-2 modifying factor (BMF). In patients with colorectal cancer, high EOMES expression (n = 95) was associated with poor overall survival compared with individuals exhibiting low EOMES levels (n = 80). We conclude from the current investigation, and prior literature, that Eomes has a divergent role in cancer development, with evidence for tumor suppressor and oncogenic functions, depending on stage and tissue context. Further studies are warranted on the apoptotic mechanisms linked to the reciprocal regulation of BMF and BIRC5 in human colorectal cancers characterized by Eomes overexpression.

Upregulation of miR-542-3p inhibits the growth and invasion of human colon cancer cells through PI3K/AKT/survivin signaling

“…Moreover, survivin indirectly inhibits caspase through P21. Its mechanism is that survivin forms the survivin-CDK4 complex with the cell cycle control factor CDK4 (23). In this way, P21 can be released from the CDK4 complex, which can further bind with mitochondrial caspase-3.…”

“…As a result, it may inhibit its activity and prevent cell apoptosis. Survivin is expressed in the G2/M phase of the cell cycle (23). At the early stage of mitosis, survivin develops a specific saturable reaction with mitotic spindle microtubule.…”

Downregulation of BIRC5 inhibits the migration and invasion of esophageal cancer cells by interacting with the PI3K/Akt signaling pathway

“…As a mitotic spindle checkpoint gene, baculoviral IAP repeat containing 5 (BIRC5) was determined to have the ability to regulate cell apoptosis (9). BIRC5 was also indicated to be involved in the onset and development of various types of malignant tumors, including breast (10), colorectal (11) and gastric cancer (12). Therefore, BIRC5 may also serve important roles in the development of esophageal cancer.…”

Exploration of immunogene in colon cancer recurrence

“…In particular, 12 of the 31 identified genes have been reported in the literatures to be related to colon cancer recurrence [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37], which can be regarded as validation to our prediction results for these 12 genes. For the other 19 genes identified by us, we cannot exclude the possibility that some of them are due to false positive prediction.…”