The role of PYCR1 in inhibiting 5-fluorouracil-induced ferroptosis and apoptosis through SLC25A10 in colorectal cancer.

IF 4.3 3区生物学 Human Cell Pub Date : 2022-11-01 Epub Date: 2022-09-14 DOI:10.1007/s13577-022-00775-5

Borong Zhou, Zhongchao Mai, Ying Ye, Yanan Song, Miao Zhang, Xinlin Yang, Wei Xia, Xiaofeng Qiu

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引用次数: 7

Abstract

Although PYCR1 is a well-recognized oncogenic gene for malignant tumors, the causal relationship of its expression with malignant growth and cytotoxic chemotherapeutics remains unclear. Therefore, this study aimed to clarify the role of PYCR1 and its interaction with SLC25A10 in a chemotherapeutic agent 5-fluorouracil (5-FU)'s toxicity to colorectal cancer cells. PYCR1 and SLC25A10 expressions were detected in The Cancer Genome Atlas database and colon adenocarcinoma (COAD) clinical samples. PYCR1 upregulation was associated with SLC25A10 expression and poor prognosis, and its high expression indicated decreased survival rates in patients with COAD. PYCR1 overexpression inhibited lipid reactive oxygen species production and promoted SLC25A10 expression in colorectal cancer cells. PYCR1 silencing enhanced the antitumor effects of 5-FU. Ferroptosis inhibitor deferoxamine suppressed the antitumor effects of PYCR1 silencing, whereas ferroptosis inducer erastin inhibited the protumor effects of PYCR1 overexpression. SLC25A10 overexpression reversed the antitumor effects of PYCR1 silencing in vitro and inhibited the antitumor effects of erastin in vivo. Therefore, PYCR1 is an oncogenic gene that promotes colorectal tumor growth and desensitizes colorectal cancer cells to 5-FU cytotoxicity by preventing apoptosis and ferroptosis.

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PYCR1在结直肠癌中通过SLC25A10抑制5-氟尿嘧啶诱导的铁氧化和细胞凋亡的作用

尽管PYCR1是一种公认的恶性肿瘤致癌基因，但其表达与恶性肿瘤生长和细胞毒性化疗的因果关系仍不清楚。因此，本研究旨在阐明PYCR1及其与SLC25A10的相互作用在化疗药物5-氟尿嘧啶（5-FU）对结直肠癌细胞的毒性中的作用。在癌症基因组图谱数据库和结肠腺癌（COAD）临床样本中检测到了PYCR1和SLC25A10的表达。PYCR1的上调与SLC25A10的表达和不良预后有关，其高表达表明COAD患者的生存率下降。PYCR1的过表达抑制了脂质活性氧的产生，促进了结直肠癌细胞中SLC25A10的表达。PYCR1沉默能增强5-FU的抗肿瘤作用。铁突变抑制剂去铁胺抑制了PYCR1沉默的抗肿瘤作用，而铁突变诱导剂麦拉宁抑制了PYCR1过表达的原癌作用。SLC25A10 的过表达逆转了体外PYCR1 沉默的抗肿瘤作用，抑制了体内麦拉宁的抗肿瘤作用。因此，PYCR1是一种致癌基因，它能促进结直肠肿瘤的生长，并通过阻止细胞凋亡和铁凋亡使结直肠癌细胞对5-FU的细胞毒性脱敏。

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来源期刊

Human Cell 生物-细胞生物学

CiteScore

6.60

自引率

2.30%

发文量

176

期刊介绍： Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well. Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format. Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.