铜死亡相关基因COX17在食管癌中的表达及其对Eca109细胞功能的影响

doi:10.3969/j.issn.1004-616x.2025.01.008

Abstract

Abstract: OBJECTIVE： To investigate expression of the cuproptosis related gene COX17，in esophageal cancer and its impact on cellular function. METHODS： Correlations between COX17 mRNA and clinical characteristics of esophageal cancer patients were evaluated using the UALCAN database. Immunohistochemistry was used to detect the expression of COX17 in 15 pairs of esophageal cancer and their corresponding adjacent tissues，and clinical pathological data was analyzed. siRNA interference was used to knock down the expression of COX17 in esophageal cancer cell line Eca109. The knockdown effect on siR-COX17 was detected by Western blot，and the effects of COX17 downregulation on the proliferation，migration，and invasion ability of Eca109 cells were detected by CCK-8 assay，scratch assay，and transwell assay. RESULTS： The UALCAN data analysis showed that，compared with the normal control group，expression of COX17 was significantly increased in esophageal cancer，and its expression level was correlated with tumor clinical stage，pathological grading，gender，age，and race (P<0.05). The immunohistochemical detection showed that the expression of COX17 was higher in esophageal cancer tissues than in corresponding adjacent tissues，and the expression level of COX17 was significantly correlated with pathological grading and lymph node metastasis (P<0.05). After siRNA transfection，the expression level of COX17 protein in Eca109 was significantly lower than that in the control group，and the knock down inhibited the proliferation，migration，and invasion ability of esophageal cancer cells. CONCLUSION： The cuproptosis related gene COX17 was highly expressed in esophageal cancer and was associated with prognosis，which mignt be involved in the malignant progression of esophageal cancer.

Key words: esophagus cancer, COX17, cuproptosis, bioinformatics

CLC Number:

R735.1

LU Wanyao, LIU Yining, SHABAHAITI·Wusiman, AI Leyu, HU Xiaowen, LI Jinglei, ZHONG Xuanyu, AIMIRELA·Mierkadier, YI Na, LIU Ling. Differential expression of copper death related gene COX17 in esophageal carcinoma and its effect on Eca109 cell function[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2025, 37(1): 45-51.

References

[1] LIU C Q, MA Y L, QIN Q, et al. Epidemiology of esophageal cancer in 2020 and projections to 2030 and 2040[J]. Thorac Cancer, 2023, 14(1): 3-11.
[2] XI Y, SHEN Y X, WU D L, et al. CircBCAR3 accelerates esophageal cancer tumorigenesis and metastasis via sponging miR-27a-3p[J]. Mol Cancer, 2022, 21(1): 145.
[3] 宋春涛, 于永洋, 高振, 等. 局部晚期食管癌免疫治疗的现状及前景[J]. 实用肿瘤杂志, 2023, 38(2): 195-201.
[4] BAO X Z, WANG Q, REN X R, et al. A hydrogen peroxide-activated Cu(II) pro-ionophore strategy for modifying naphthazarin as a promising anticancer agent with high selectivity for generating ROS in HepG2 cells over in L02 cells[J]. Free Radic Biol Med, 2020, 152: 597-608.
[5] COBINE P A, BRADY D C. Cuproptosis: Cellular and molecular mechanisms underlying copper-induced cell death[J]. Mol Cell, 2022, 82(10): 1786-1787.
[6] YU M L, REN L X, ZHENG M X, et al. Delayed diagnosis of Wilson’s disease report from 179 newly diagnosed cases in China[J]. Front Neurol, 2022, 13: 884840.
[7] GUO Y, XIA W, PENG X H, et al. Almost misdiagnosed Menkes disease: a case report[J]. Heliyon, 2022, 8(4): e09268.
[8] TSVETKOV P, COY S, PETROVA B, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins[J]. Science, 2022, 375(6586): 1254-1261.
[9] ZHANG M, SHI M, ZHAO Y. Association between serum copper levels and cervical cancer risk: a meta-analysis[J]. Biosci Rep, 2018, 38(4): BSR20180161.
[10] ZHANG X P, YANG Q. Association between serum copper levels and lung cancer risk: a meta-analysis[J]. J Int Med Res, 2018, 46(12): 4863-4873.
[11] FENG Y, ZENG J W, MA Q, et al. Serum copper and zinc levels in breast cancer: a meta-analysis[J]. J Trace Elem Med Biol, 2020, 62: 126629.
[12] ATAKUL T, ALTINKAYA S O, ABAS B I, et al. Serum copper and zinc levels in patients with endometrial cancer[J]. Biol Trace Elem Res, 2020, 195(1): 46-54.
[13] PALUMAA P, KANGUR L, VORONOVA A, et al. Metal-binding mechanism of Cox17, a copper chaperone for cytochrome c oxidase[J]. Biochem J, 2004, 382(Pt 1): 307-314.
[14] MAXFIELD A B, HEATON D N, WINGE D R. Cox17 is functional when tethered to the mitochondrial inner membrane[J]. J Biol Chem, 2004, 279(7): 5072-5080.
[15] PRUSINKIEWICZ M A, GAMEIRO S F, GHASEMI F, et al. Survival-associated metabolic genes in human papillomavirus-positive head and neck cancers[J]. Cancers, 2020, 12(1): 253.
[16] SUZUKI C, DAIGO Y, KIKUCHI T, et al. Identification of COX17 as a therapeutic target for non-small cell lung cancer[J]. Cancer Res, 2003, 63(21): 7038-7041.
[17] SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[18] XUE Q, KANG R, KLIONSKY D J, et al. Copper metabolism in cell death and autophagy[J]. Autophagy, 2023, 19(8): 2175-2195.
[19] CHEN L Y, MIN J X, WANG F D. Copper homeostasis and cuproptosis in health and disease[J]. Signal Transduct Target Ther, 2022, 7: 378.
[20] ZHU S Y, ZHOU W Q, NIU Y Y, et al. COX17 restricts renal fibrosis development by maintaining mitochondrial copper homeostasis and restoring complex IV activity[J]. Acta Pharmacol Sin, 2023, 44(10): 2091-2102.
[21] 沙巴海提·吾斯曼, 伊娜, 刘志琴, 等. 铜死亡相关基因COX17在乳腺癌组织和细胞中的表达及其与临床特征和患者预后的关系[J]. 中国肿瘤生物治疗杂志, 2023, 30(12): 1088-1098.
[22] HUANG D B, CHEN L X, JI Q Y, et al. Lead aggravates Alzheimer--s disease pathology via mitochondrial copper accumulation regulated by COX17[J]. Redox Biol, 2024, 69: 102990.
[23] VANI-OVá M, BURSKá D, K-í-OVá J, et al. Stable COX17 downregulation leads to alterations in mitochondrial ultrastructure, decreased copper content and impaired cytochrome c oxidase biogenesis in HEK293 cells[J]. Folia Biol, 2019, 65(4): 181-187.

Differential expression of copper death related gene COX17 in esophageal carcinoma and its effect on Eca109 cell function

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