Hypoxia-induced the upregulation of NDUFA4L2 promoted colon adenocarcinoma progression through ROS-mediated PI3K/AKT pathway.

IF 2 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Cytotechnology Pub Date : 2023-12-01 Epub Date: 2023-09-19 DOI:10.1007/s10616-023-00590-2
Nianyuan Ye, Yibo Wang, Peng Jiang, Huaji Jiang, Wei Ding, Zheng Zhang, Cheng Xi
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引用次数: 0

Abstract

The NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) gene has been reported to be upregulated in colorectal cancer (CRC) and is associated with worse prognosis. However, the specific function and underlying mechanism of NDUFA4L2 in colon adenocarcinoma (COAD) under hypoxia has never been investigated. Our study discovered that hypoxia promoted the viability, metastasis, and epithelial-mesenchymal transition (EMT) of COAD cells. Besides, hypoxia-induced HIF-1α upregulated the expression of NDUFA4L2 which served as an oncogene and an independent diagnostic and prognostic marker in COAD. Under hypoxic environment, NDUFA4L2 mediated the viability, metastasis, and epithelial-EMT of COAD cells. Additionally, the ROS-dependent PI3K/Akt signaling was activated by NDUFA4L2 in COAD in hypoxia and NDUFA4L2 facilitated the malignant behaviors of hypoxia-treated COAD cells by elevating ROS production. Collectively, abundant NDUFA4L2 expression induced by HIF-1α under hypoxia promoted the development of COAD through activation of the PI3K/AKT signaling in a ROS-dependent manner, indicating NDUFA4L2 as a promising target in COAD diagnosis and treatment.

Abstract Image

缺氧诱导NDUFA4L2的上调通过ROS介导的PI3K/AKT途径促进结肠腺癌的进展。
据报道,NADH脱氢酶(泛醌)1α亚复合体4样2(NDUFA4L2)基因在癌症(CRC)中上调,并与更差的预后相关。然而,NDUFA4L2在缺氧条件下结肠癌(COAD)中的特异性功能和潜在机制尚未得到研究。我们的研究发现,缺氧促进了COAD细胞的生存能力、转移和上皮-间质转化(EMT)。此外,缺氧诱导的HIF-1α上调了NDUFA4L2的表达,NDUFA4L2是COAD的致癌基因和独立的诊断和预后标志物。在低氧环境下,NDUFA4L2介导COAD细胞的生存能力、转移和上皮EMT。此外,缺氧时COAD中的NDUFA4L2激活了ROS依赖性PI3K/Akt信号传导,NDUFA4L2通过提高ROS的产生促进了缺氧处理的COAD细胞的恶性行为。总之,缺氧条件下HIF-1α诱导的大量NDUFA4L2表达通过激活PI3K/AKT信号以ROS依赖的方式促进了COAD的发展,表明NDUFA4L2是COAD诊断和治疗中有前途的靶点。
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来源期刊
Cytotechnology
Cytotechnology 生物-生物工程与应用微生物
CiteScore
4.10
自引率
0.00%
发文量
49
审稿时长
6-12 weeks
期刊介绍: The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.
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