ICT1 Promotes Osteosarcoma Cell Proliferation and Inhibits Apoptosis via STAT3/BCL-2 Pathway

Abstract

Osteosarcoma (OS) is a familiar malignant bone tumor that occurs mainly in adolescents. Immature colon carcinoma transcript-1 (ICT1) is an important member of the large mitoribosomal subunit in mitochondrial ribosomes, which has been shown to be closely related to tumorigenesis. Its expression and function in OS, however, remained unclear. Here, we showed that ICT1 was significantly upregulated in OS and promoted the growth of OS cells. Mechanistically, ICT1 acted as an oncogene in OS and promoted proliferation and inhibited apoptosis of OS cells through the STAT3/BCL-2 axis. These results reveal a novel insight into the role of the ICT1/STAT3/BCL-2 axis in OS and therefore may represent a novel molecular target for novel treatments.

Functional Diversity of Mitochondrial Peptidyl-tRNA Hydrolase ICT1 in Human Cells

“…In addition, depletion of ICT1 suppresses the migration of colorectal cancer cells (Lao et al, 2016) and gastric cancer cells (Tao et al, 2017), while its overexpression respectively leads to an increase in their mobility. Interestingly, the growth and division of non-cancerous cells, for example, osteoblasts, practically do not change upon ICT1 knockdown (Pan et al, 2021); therefore, the described phenomena are specific to tumor cells.…”

“…As we mentioned earlier, ICT1 was first discovered in the study of cancer markers and further its role in oncogenesis was actively investigated. Overexpression of ICT1 has been reported in many types of malignancies such as glioblastoma (Xie et al, 2015), diffuse large B cell lymphoma (Xie et al, 2017), colorectal cancer (Lao et al, 2016) prostate cancer (Wang et al, 2015), breast cancer (Chen et al, 2017;Peng et al, 2018), hepatocellular carcinoma (Chang et al, 2017), leukemia (Li et al, 2018), lung cancer (Huang et al, 2014;Wang et al, 2017a) and osteosarcoma (Pan et al, 2021). These data, obtained by various methods, such as RT-qPCR, Western blotting, and immunohistochemistry, make it possible to classify ICT1 as an oncogene and use it as a marker for medical diagnostics.…”

“…These data, obtained by various methods, such as RT-qPCR, Western blotting, and immunohistochemistry, make it possible to classify ICT1 as an oncogene and use it as a marker for medical diagnostics. Interestingly, a number of studies have demonstrated a negative correlation between the level of ICT1 expression in tumors and patient survival, as well as its relationship with the clinical manifestations of the disease (Lao et al, 2016;Chang et al, 2017;Xie et al, 2017;Pan et al, 2021). According to clinical statistics, the protein content was higher in large, late and metastatic tumors (Chang et al, 2017;Xie et al, 2017;Pan et al, 2021).…”

“…Interestingly, a number of studies have demonstrated a negative correlation between the level of ICT1 expression in tumors and patient survival, as well as its relationship with the clinical manifestations of the disease (Lao et al, 2016;Chang et al, 2017;Xie et al, 2017;Pan et al, 2021). According to clinical statistics, the protein content was higher in large, late and metastatic tumors (Chang et al, 2017;Xie et al, 2017;Pan et al, 2021). Thus, a high content of ICT1 can indicate an aggressive development of the disease, an unfavorable prognosis, and high risks to the life and health of the patient.…”

“…Violation of this program largely determines the transformation of a cell into a cancerous one. The role of ICT1 in the regulation of apoptosis has been shown in a large number of studies carried out on various types of cancer cells, which allows considering it as a universal mechanism (Wang et al, 2015;Lao et al, 2016;Wang et al, 2017a;Wang et al, 2017b;Chang et al, 2017;Chen et al, 2017;Xie et al, 2017;Li et al, 2018;Pan et al, 2021). The high ICT1 content in cancer cells inhibits apoptosis, and its reduction through knockdown activates the "cellular suicide program."…”