<p>Cytochrome C Oxidase Assembly Factor 1 Homolog Predicts Poor Prognosis and Promotes Cell Proliferation in Colorectal Cancer by Regulating PI3K/AKT Signaling</p>

Abstract

Purpose Colorectal cancer (CRC) is one of the most common malignancies in the world. The prognosis of advanced CRC is still poor. The purpose of this study was to identify a gene expression profile associated with CRC that may contribute to the early diagnosis of CRC and improve patient prognosis. Patients and Methods Five pairs of CRC tissues and paracancerous tissues were used to identify causative genes using microarray assays. The prognostic value of Cytochrome C Oxidase Assembly Factor 1 Homolog (COA1) in CRC was assessed in 90 CRC patients. Loss-of-function assays, cell proliferation assays using Celigo and MTT, colony formation assays, a subcutaneous xenograft mouse model, and apoptosis assays were used to define the effects of downregulation of COA1 in CRC cells in vitro and in vivo. The underlying molecular mechanisms of COA1 in CRC were also investigated. Results The causative gene COA1 was identified through microarray analysis. COA1 expression in CRC was notably associated with pathologic differentiation, tumor size, and tumor depth. COA1 expression may act as an independent prognostic factor for overall survival of CRC. Knockdown of COA1 inhibited the proliferation of CRC cells in vitro and the tumorigenicity of CRC cells in vivo. Decreased COA1 expression induced apoptosis of CRC cells. Based on the microarray assay results comparing HCT116 cells transfected with lentivirus encoding anti-COA1 shRNA or negative control shRNA, ingenuity pathway analysis (IPA) revealed that the PI3K/AKT signaling pathway was significantly enriched. Moreover, CCND1, mTOR, AKT1, and MDM2 were identified as the downstream genes of COA1. Conclusion These findings demonstrate that COA1 promotes CRC cell proliferation and inhibits apoptosis by regulating the PI3K/AKT signaling pathway. Our results implicate COA1 as a potential oncogene involved in tumor growth and progression of CRC.

MicroRNA‑23b‑3p targets non‑SMC condensing I complex subunit G to promote proliferation and inhibit apoptosis of colorectal cancer cells via regulation of the PI3K/AKT signaling pathway

“…Accumulating evidence has revealed that the upregulated expression of NCAPG is associated with several types of malignant tumor, including gastric cancer ( 6 – 7 ), HCC ( 9 ) and ovarian cancer ( 10 ). The results of the current study demonstrated that the expression levels of NCAPG were upregulated in CRC tissues and cell lines, which is consistent with the findings of our previous study ( 11 ). In another previous study, upregulated NCAPG expression was found to be associated with TNM stage, distant metastasis, nodal status and vascular invasion in gastric cancer ( 6 ).…”

“…Over the past few years, an accumulating number of studies have reported that NCAPG is involved in the pathogenesis of various types of cancer, including breast ( 5 ), gastric ( 6 , 7 ) and prostate cancer ( 8 ), hepatocellular carcinoma (HCC) ( 9 ) and ovarian cancer ( 10 ). In our previous study, gene microarray analysis revealed that the expression levels of NCAPG were upregulated in CRC specimens ( 11 ). However, to the best of our knowledge, the biological functions and clinical implications of NCAPG in CRC remain to be determined.…”

Evaluation of potential anti-metastatic and antioxidative abilities of natural peptides derived from Tecoma stans (L.) Juss. ex Kunth in A549 cells

“…Although the cancer-based study of COA4, a mediator protein in the assembly process of the cytochrome c oxidase complex ( Watson & McStay, 2020 ), is lacking, overexpression of its related protein (COA1) has also been shown in colorectal cancer. The microarray assay showed that overexpression of COA1 in colorectal cancer tissues is associated with poor prognosis, and suppression of COA1 expression reduces the growth of colorectal cancer cell lines ( Xue et al, 2020 ). Here, we showed that natural peptides from T. stans inhibited the growth, migration and invasion of A549 cells by suppressing the expression of cancer-promoting proteins (NCBP2, AMD, MER34, ENC1, and COA4).…”

Recurrent erosion ofCOA1/MITRAC15demonstrates gene dispensability in oxidative phosphorylation

“…While specific genetic changes in mammalian species lead to cancer resistance (Tollis et al, 2019; Vazquez et al, 2018), the reasons for lower cancer incidence in birds compared to mammals are mostly unexplored (Møller et al, 2017). Interestingly, the COA1/MITRAC15 gene is an oncogene with a role in colorectal cancer (Xue et al, 2020), and its loss could reduce cancer risk. Silencing of COA1/MITRAC15 by miRNAs strongly suppresses Giant cell tumors of the bone (Fellenberg et al, 2016; Herr et al, 2017).…”