Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (5): 74-80.doi: 10.6040/j.issn.1671-7554.0.2021.1475

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Expression of aryl hydrocarbon receptor nuclear translocator-like 2 in endometrial cancer

SHEN Xiaochang1, SUN Yiqing1, YAN Lei2, ZHAO Xingbo1   

  1. 1. Department of Gynecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China;
    2. Department of Gynecology, Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan 250001, Shandong, China
  • Published:2022-06-01

Abstract: Objective To explore the expression and function of aryl hydrocarbon receptor nuclear translocator-like 2(ARNTL2)in endometrial cancer(EC)and its possible signal pathway. Methods The expression of ARNTL2 in EC and normal tissues was detected with immunohistochemistry, RT-PCR and Western blotting. After ARNTL2 knock down with Si-RNA(Si-ARNTL2), cell proliferation, invasion and migration were detected with CCK-8 assay, scratch healing test and Transwell assay, respectively. The epithelial-mesenchymal transition(EMT)indicators, including E-cad, N-cad, Vimentin, Snail and Slug, and Wnt/β-catenin signal pathway related proteins, including Wnt and β-catenin, were detected with Western blotting. Results Immunohistochemistry, RT-PCR and Western blotting showed that the expression of ARNTL2 was up-regulated in EC tissue(tImmunohistochemistry=2.213, P=0.033; tRT-PCR=4.766, P<0.001; tWestern blotting=2.659, P=0.012). Si-ARNTL2 transfection successfully reduced ARNTL2 expression in EC cell lines(KLE and Ishikawa). After knockdown of ARNTL2, CCK8 assay showed reduction in the absorbance of both cell lines(P<0.05); Scratch healing test showed a suppression on wound healing rate(P<0.001); Transwell invasion and migration assay showed that the number of transmembrane cells decreased(P<0.01). Western blotting showed that the expression of E-cad in the two cell lines increased, while the expressions of N-cad, Vimentin, Snail and Slug decreased(P<0.05), and the expressions of Wnt and β-catenin decreased(P<0.05). Conclusion The expression of ARNTL2 is higher in EC tissue than in normal tissue. Knockdown of ARNTL2 can inhibit cell proliferation and metastasis in EC. ARNTL2 may promote tumor proliferation and metastasis through Wnt/β-catenin pathway.

Key words: Aryl hydrocarbon receptor nuclear translocator-like 2, Endometrial cancer, Proliferation, Metastasis, Epithelial-mesenchymal transition, Signal pathway

CLC Number: 

  • R737.33
[1] Morice P, Leary A, Creutzberg C, et al. Endometrial cancer [J]. Lancet, 2016, 387(10023): 1094-1108.
[2] Siegel RL, Miller KD, Fuchs HE. Cancer statistics, 2021 [J]. CA Cancer J Clin, 2021, 71(1): 7-33.
[3] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020 [J]. CA Cancer J Clin, 2020, 70(1): 7-30.
[4] Wu H, Dunnett S, Ho YS, et al. The role of sleep deprivation and circadian rhythm disruption as risk factors of Alzheimers disease [J]. Front Neuroendocrinol, 2019, 54: 100764. doi:10.1016/j.yfrne.2019.100764.
[5] Zhou J, Wang J, Zhang X, et al. New insights into cancer chronotherapies [J]. Front Pharmacol, 2021, 12: 741295. doi:10.3389/fphar.2021.741295.
[6] 中国抗癌协会妇科肿瘤专业委员会.子宫内膜癌诊断与治疗指南(2021年版)[J]. 中国癌症杂志, 2021, 31(6): 501-512.
[7] Lu KH, Broaddus RR. Endometrial cancer [J]. N Engl J Med, 2020, 383(21): 2053-2064.
[8] Gery S, Koeffler HP. Circadian rhythms and cancer [J]. Cell Cycle, 2010, 9(6): 1097-1103.
[9] Crespo M, Leiva M, Sabio G. Circadian clock and liver cancer [J]. Cancers(Basel), 2021, 13(14): 3631. doi: 10.3390/cancers13143631.
[10] Yeh KT, Yang MY, Liu TC, et al. Abnormal expression of period 1(PER1)in endometrial carcinoma [J]. J Pathol, 2005, 206(1): 111-120.
[11] Wang Z, Wang H, Wang Z, et al. Associated analysis of PER1/TUBB2B with endometrial cancer development caused by circadian rhythm disorders [J]. Med Oncol, 2020, 37(10): 90. doi:10.1007/s12032-020-01415-4.
[12] Shih MC, Yeh KT, Tang KP, et al. Promoter methylation in circadian genes of endometrial cancers detected by methylation-specific PCR [J]. Mol Carcinog, 2006, 45(10): 732-740.
[13] Takeda N, Maemura K, Horie S, et al. Thrombomodulin is a clock-controlled gene in vascular endothelial cells [J]. J Biol Chem, 2007, 282(45): 32561-32567.
[14] Wang Y, Peng S, Liu T, et al. The potential role of clock genes in children attention-deficit/hyperactivity disorder [J]. Sleep Med, 2020, 71: 18-27. doi: 10.1016/j.sleep.2020.02.021.
[15] Barbosa Vieira TK, Jurema da Rocha Leão M, Pereira LX, et al. Correlation between circadian rhythm related genes, type 2 diabetes, and cancer: insights from metanalysis of transcriptomics data [J]. Mol Cell Endocrinol, 2021, 526: 111214. doi:10.1016/j.mce.2021.111214.
[16] Shi SQ, Ansari TS, McGuinness OP, et al. Circadian disruption leads to insulin resistance and obesity [J]. Curr Biol, 2013, 23(5): 372-381.
[17] Azevedo PG, Miranda LR, Nicolau ES, et al. Genetic association of the PERIOD3(PER3)clock gene with extreme obesity [J]. Obes Res Clin Pract, 2021, 15(4): 334-338.
[18] Lu M, Huang L, Tang Y, et al. ARNTL2 knockdown suppressed the invasion and migration of colon carcinoma: decreased SMOC2-EMT expression through inactivation of PI3K/AKT pathway [J]. Am J Transl Res, 2020, 12(4): 1293-1308.
[19] Brady JJ, Chuang CH, Greenside PG, et al. An arntl2-driven secretome enables lung adenocarcinoma metastatic self-sufficiency [J]. Cancer Cell, 2016, 29(5): 697-710.
[20] Wang Z, Liu T, Xue W, et al. ARNTL2 promotes pancreatic ductal adenocarcinoma progression through TGF/BETA pathway and is regulated by miR-26a-5p [J]. Cell Death Dis, 2020, 11(8): 692. doi:10.1038/s41419-020-02839-6.
[21] Ha NH, Long J, Cai Q, et al. The circadian rhythm gene Arntl2 is a metastasis susceptibility gene for estrogen receptor-negative breast cancer [J]. PLoS Genet, 2016, 12(9): e1006267. doi:10.1371/journal.pgen.1006267.
[22] Pan G, Liu Y, Shang L, et al. EMT-associated microRNAs and their roles in cancer stemness and drug resistance [J]. Cancer Commun(Lond), 2021, 41(3): 199-217.
[23] Usman S, Waseem NH, Nguyen TKN, et al. Vimentin is at the heart of epithelial mesenchymal transition(EMT)mediated metastasis [J]. Cancers(Basel), 2021, 13(19): 4985. doi: 10.3390/cancers13194985.
[24] Lei Y, Chen L, Zhang G, et al. MicroRNAs target the Wnt/β-catenin signalling pathway to regulate epithelial-mesenchymal transition in cancer(Review)[J]. Oncol Rep, 2020, 44(4): 1299-1313.
[25] Rao TP, Kühl M. An updated overview on wnt signalling pathways: a prelude for more [J]. Circ Res, 2010, 106(12): 1798-1806.
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