Knockdown of ISOC1 inhibits the proliferation and migration and induces the apoptosis of colon cancer cells through the AKT/GSK-3β pathway.

Abstract

Isochorismatase domain-containing 1 (ISOC1) is a coding gene that contains an isochorismatase domain. The precise functions of ISOC1 in humans have not been clarified; however, studies have speculated that it may be involved in unknown metabolic pathways. Currently, it is reported that ISOC1 is associated with breast cancer. In this research, the aim is to investigate the critical role of ISOC1 in colorectal cancer (CRC) and to explore its biological function and mechanism in colon cancer cells. In 106 paired clinical samples, we found that the levels of ISOC1 expression were widely increased in cancer tissues compared with matched adjacent non-tumor tissues and that increased expression of ISOC1 was significantly associated with tumor size, tumor invasion, local lymph node metastasis and Tumor, Node and Metastasis (TNM) stage. Moreover, higher expression levels of ISOC1 were correlated with shorter disease-free survival in patients 2 years after surgery. In vitro, ISOC1 knockdown inhibited the proliferation and migration and induced the apoptosis of colon cancer cells, and in vivo, the xenograft tumors were also inhibited by ISOC1 silencing. We also used MTS, Transwell and cell apoptosis assays to confirm that ISOC1 plays a critical role in regulating the biological functions of colon cancer cells through the AKT/GSK-3β pathway. Additionally, the results of confocal microscopy and western blot analysis indicated that ISOC1 knockdown could promote p-STAT1 translocation to the nucleus.

• Authors: Bo Gao, Lianmei Zhao, Feifei Wang, Hanyu Bai, Jing Li, Meng Li, Xuhua Hu, Jian Cao, Guiying Wang
• Journal: Carcinogenesis (Carcinogenesis) Vol. 41 Issue 8 Pg. 1123-1133 (08 12 2020) ISSN: 1460-2180 [Electronic] England
• PMID: 31740942 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2019. Published by Oxford University Press.

Chemical References

• STAT1 Transcription Factor
• STAT1 protein, human
• Glycogen Synthase Kinase 3 beta
• Proto-Oncogene Proteins c-akt

Topics

• Active Transport, Cell Nucleus
• Animals
• Apoptosis (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Colorectal Neoplasms (genetics, pathology)
• Gene Knockdown Techniques
• Glycogen Synthase Kinase 3 beta (genetics, metabolism)
• Heterografts
• Humans
• Male
• Mice, Inbred BALB C
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• STAT1 Transcription Factor (metabolism)
• Signal Transduction