Abstract
The aim of this study is to investigate the role of CDGSH iron-sulfur domain 2 (CISD2) in colorectal cancer (CRC). The purpose of this study was to investigate the role of CDGSH iron-sulfur domain 2 (CISD2) in colorectal cancer (CRC) progression. The expression of CISD2 in CRC cell lines was measured by western blotting. Functional assays including MTT assays and colony formation assays were performed to explore the role of CISD2 in regulating tumor growth. Flow cytometry analysis was used to examine the percentage of apoptotic CRC cells. Expression of apoptosis-related gene, autophagy-related markers, and the protein included in Wnt/β-Catenin signaling was also determined by western blotting. The in vivo role of CISD2 was also examined in a xenograft model. CISD2 expression was significantly increased in CRC cells. CISD2 promoted the CRC cell proliferation and inhibited the apoptosis and autophagy of CRC cells. Moreover, knockdown of CISD2 inhibited the activation of Wnt/β-Catenin-signaling pathway. Knockdown of CISD2 inhibited the tumor growth in nude mice. CISD2 promoted colorectal cancer development by inhibiting CRC cell apoptosis and autophagy depending on activating Wnt/β-Catenin-signaling pathway.
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References
Buikhuisen JY, Torang A, Medema JP (2020) Exploring and modelling colon cancer inter-tumour heterogeneity: opportunities and challenges. Oncogenesis 9:66. https://doi.org/10.1038/s41389-020-00250-6
Chang NC, Nguyen M, Shore GC (2012) BCL2-CISD2: An ER complex at the nexus of autophagy and calcium homeostasis? Autophagy 8:856–857. https://doi.org/10.4161/auto.20054
Clevers H, Nusse R (2012) Wnt/β-catenin signaling and disease. Cell 149:1192–1205. https://doi.org/10.1016/j.cell.2012.05.012
He C, Wang L, Zhang J, Xu H (2017) Hypoxia-inducible microRNA-224 promotes the cell growth, migration and invasion by directly targeting RASSF8 in gastric cancer. Mol Cancer 16:35. https://doi.org/10.1186/s12943-017-0603-1
Li SM, Chen CH, Chen YW, Yen YC, Fang WT, Tsai FY et al (2017) Upregulation of CISD2 augments ROS homeostasis and contributes to tumorigenesis and poor prognosis of lung adenocarcinoma. Sci Rep 7:11893. https://doi.org/10.1038/s41598-017-12131-x
Lin J, Zhang L, Lai S, Ye K (2011) Structure and molecular evolution of CDGSH iron-sulfur domains. PLoS ONE 6:e24790. https://doi.org/10.1371/journal.pone.0024790
Liu L, Zhang Y, Wong CC, Zhang J, Dong Y, Li X et al (2018) RNF6 promotes colorectal cancer by activating the Wnt/β-Catenin pathway via ubiquitination of TLE3. Cancer Res 78:1958–1971. https://doi.org/10.1158/0008-5472.can-17-2683
Lorzadeh S, Kohan L, Ghavami S, Azarpira N (2021) Autophagy and the Wnt signaling pathway: a focus on Wnt/β-catenin signaling. Biochim Biophys Acta Mol Cell Res 1868:118926. https://doi.org/10.1016/j.bbamcr.2020.118926
Mármol I, Sánchez-de-Diego C, Pradilla Dieste A, Cerrada E, Rodriguez Yoldi MJ (2017) Colorectal carcinoma: a general overview and future perspectives in colorectal cancer. Int J Mol Sci. https://doi.org/10.3390/ijms18010197
Molinari C, Marisi G, Passardi A, Matteucci L, De Maio G, Ulivi P (2018) Heterogeneity in colorectal cancer: a challenge for personalized medicine? Int J Mol Sci. https://doi.org/10.3390/ijms19123733
Paddock ML, Wiley SE, Axelrod HL, Cohen AE, Roy M, Abresch EC et al (2007) MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone. Proc Natl Acad Sci USA 104:14342–14347. https://doi.org/10.1073/pnas.0707189104
Shen ZQ, Chen YF, Chen JR, Jou YS, Wu PC, Kao CH et al (2017) CISD2 haploinsufficiency disrupts calcium homeostasis, causes nonalcoholic fatty liver disease, and promotes hepatocellular carcinoma. Cell Rep 21:2198–2211. https://doi.org/10.1016/j.celrep.2017.10.099
Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC et al (2020) Colorectal cancer statistics, 2020. CA Cancer J Clin 70:145–164. https://doi.org/10.3322/caac.21601
Sun AG, Meng FG, Wang MG (2017a) CISD2 promotes the proliferation of glioma cells via suppressing beclin-1-mediated autophagy and is targeted by microRNA-449a. Mol Med Rep 16:7939–7948. https://doi.org/10.3892/mmr.2017.7642
Sun Y, Jiang Y, Huang J, Chen H, Liao Y, Yang Z (2017b) CISD2 enhances the chemosensitivity of gastric cancer through the enhancement of 5-FU-induced apoptosis and the inhibition of autophagy by AKT/mTOR pathway. Cancer Med 6:2331–2346. https://doi.org/10.1002/cam4.1169
Taciak B, Pruszynska I, Kiraga L, Bialasek M, Krol M (2018) Wnt signaling pathway in development and cancer. J Physiol Pharmacol. https://doi.org/10.26402/jpp.2018.2.07
Tompkins KD, Thorburn A (2019) Regulation of apoptosis by autophagy to enhance cancer therapy. Yale J Biol Med 92:707–718
Wang L, Ouyang F, Liu X, Wu S, Wu HM, Xu Y et al (2016) Overexpressed CISD2 has prognostic value in human gastric cancer and promotes gastric cancer cell proliferation and tumorigenesis via AKT signaling pathway. Oncotarget 7:3791–3805. https://doi.org/10.18632/oncotarget.6302
Xie YH, Chen YX, Fang JY (2020) Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct Target Ther 5:22. https://doi.org/10.1038/s41392-020-0116-z
Yang L, Hong S, Wang Y, He Z, Liang S, Chen H et al (2016) A novel prognostic score model incorporating CDGSH iron sulfur domain2 (CISD2) predicts risk of disease progression in laryngeal squamous cell carcinoma. Oncotarget 7:22720–22732. https://doi.org/10.18632/oncotarget.8150
Yang Y, Bai YS, Wang Q (2017) CDGSH iron sulfur domain 2 activates proliferation and EMT of pancreatic cancer cells via Wnt/β-Catenin pathway and has prognostic value in human pancreatic cancer. Oncol Res 25:605–615. https://doi.org/10.3727/096504016x14767450526417
Zhan T, Rindtorff N, Boutros M (2017) Wnt signaling in cancer. Oncogene 36:1461–1473. https://doi.org/10.1038/onc.2016.304
Zhang Y, Wang X (2020) Targeting the Wnt/β-catenin signaling pathway in cancer. J Hematol Oncol 13:165. https://doi.org/10.1186/s13045-020-00990-3
Zhu QQ, Tian L, Li DL, Wu ZH, He YY, Zhang HK (2020) Elevated CISD2 expression predicts poor diagnosis and promotes invasion and migration of prostate cancer cells. Eur Rev Med Pharmacol Sci 24:6597–6604. https://doi.org/10.26355/eurrev_202006_21645
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This work was supported by the 2014 Medical Clinical Science and Technology Development Fund of Jiangsu University (Grant No. JLY201440087).
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JW and JH designed the study, supervised the data collection, MW and HY analyzed the data, interpreted the data, YX, XZ, MD, WC, BQ, and LZ prepare the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript.
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All animal experiments were approved by the Ethics Committee of Gaochun People’s Hospital. For the use of animals and conducted in accordance with the National Institutes of Health Laboratory Animal Care and Use Guidelines.
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Wang, J., Hu, J., Wang, M. et al. CISD2 Promotes Proliferation of Colorectal Cancer Cells by Inhibiting Autophagy in a Wnt/β-Catenin-Signaling-Dependent Pathway. Biochem Genet 61, 615–627 (2023). https://doi.org/10.1007/s10528-022-10267-8
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DOI: https://doi.org/10.1007/s10528-022-10267-8