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Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells

  • Authors:
    • Lu Ma
    • Xin Li
    • Xiaopeng Zhao
    • Haotong Sun
    • Feifei Kong
    • Yuanjie Li
    • Yu Sui
    • Fang Xu
  • View Affiliations / Copyright

    Affiliations: Department of Medical Genetics and Cell Biology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, Department of Oncology, Qufu People's Hospital, Qufu, Shandong 273100, P.R. China
    Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 629
    |
    Published online on: July 5, 2021
       https://doi.org/10.3892/mmr.2021.12268
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Abstract

The clinical efficacy of colorectal tumor treatment is restricted due to platinum agent resistance. Translesion DNA synthesis (TLS) has been shown to contribute to this resistance; however, the exact molecular mechanism remains unknown. The present study aimed to investigate the possible function of the core of the TLS polymerase mitotic arrest deficient 2 like 2 (MAD2L2) in drug sensitivity, in order to provide a treatment rationale for platinum‑based chemotherapy in colon cancer. In the present study, MAD2L2 was knocked down using MAD2L2‑specific small interfering (si)RNA. HCT116 and SW620 cells were treated with oxaliplatin and MG132; oxaliplatin is a platinum compound that induces DNA damage and MG132 is a potent proteasome inhibitor. Cell viability was determined using an MTT assay. Cell apoptosis was examined via flow cytometry and TUNEL assay. The activity of proteasome 26S subunit, non‑ATPase 13 (PSMD13) was detected using ELISA, while the expression levels of apoptotic‑related proteins were detected via western blotting. The results demonstrated that cells treated with oxaliplatin or MG132 alone had decreased viability, but a synergistic effect was not observed after co‑treatment. In addition, the knockdown of MAD2L2 caused by siMAD2L2 or oxaliplatin treatment increased the expression levels of the pro‑apoptotic proteins Bax and Bak and decreased the expression levels of the anti‑apoptotic protein Bcl‑2, compared with the negative control group. Moreover, MG132 alleviated the decrease in MAD2L2 expression, while reducing siMAD2L2‑induced cell apoptosis. These results indicate that oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells. This process was associated with the Bcl‑2 and ubiquitin‑proteasome pathway. Overall, the present study provides a theoretical basis for improving the clinical efficacy of colon cancer by combining chemotherapy and gene therapy.
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1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2020. CA Cancer J Clin. 70:7–30. 2020. View Article : Google Scholar : PubMed/NCBI

2 

Crowley LC, Marfell BJ and Waterhouse NJ: Detection of DNA fragmentation in apoptotic cells by TUNEL. Cold Spring Harb Protoc. 20162016.

3 

Zhou J, Zheng R, Zhang S, Zeng H, Wang S, Chen R, Sun K, Li M, Gu J, Zhuang G and Wei W: Colorectal cancer burden and trends: Comparison between China and major burden countries in the world. Chin J Cancer Res. 33:1–10. 2021. View Article : Google Scholar : PubMed/NCBI

4 

National Health Commission Of The People's Republic Of China, . National guidelines for diagnosis and treatment of colorectal cancer 2020 in China (English version). Chin J Cancer Res. 32:415–445. 2020. View Article : Google Scholar : PubMed/NCBI

5 

Sharma G, Anghore D, Khare R and Rawal RK: Oxaliplatin for colorectal cancer therapy: A review. Clin Cancer Drugs. 5:13–27. 2018. View Article : Google Scholar : PubMed/NCBI

6 

Brown A, Kumar S and Tchounwou PB: Cisplatin-based chemotherapy of human cancers. J Cancer Sci Ther. 11:972019.PubMed/NCBI

7 

McQuade RM, Stojanovska V, Bornstein JC and Nurgali K: Colorectal cancer chemotherapy: The evolution of treatment and new approaches. Curr Med Chemistry. 24:1537–1557. 2017. View Article : Google Scholar : PubMed/NCBI

8 

Sigel A, Riddell IA, Lippard SJ, Sigel H, Freisinger E and Sigel RKO: Cisplatin and oxaliplatin: Our current understanding of their actions. 1–42. 2018.PubMed/NCBI

9 

Ma X, Tang TS and Guo C: Regulation of translesion DNA synthesis in mammalian cells. Environ Mol Mutagen. 61:680–692. 2020. View Article : Google Scholar : PubMed/NCBI

10 

Shanbhag V, Sachdev S, Flores JA, Modak MJ and Singh K: Family A and B DNA polymerases in cancer: Opportunities for therapeutic interventions. Biology (Basel). 7:52018.PubMed/NCBI

11 

Sharma S, Shah NA, Joiner AM, Roberts KH and Canman CE: DNA polymerase zeta is a major determinant of resistance to platinum-based chemotherapeutic agents. Mol Pharmacol. 81:778–787. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Jiang HG, Chen P, Su JY, Wu M, Qian H, Wang Y and Li J: Knockdown of REV3 synergizes with ATR inhibition to promote apoptosis induced by cisplatin in lung cancer cells. J Cell Physiol. 232:3433–3443. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Malik R, Kopylov M, Gomez-Llorente Y, Jain R, Johnson RE, Prakash L, Prakash S, Ubarretxena-Belandia I and Aggarwal AK: Structure and mechanism of B-family DNA polymerase zeta specialized for translesion DNA synthesis. Nat Struct Mol Biol. 27:913–924. 2020. View Article : Google Scholar : PubMed/NCBI

14 

Washington MT and Gildenberg MS: Structure of DNA polymerase ζ: Capturing the getaway driver. Nat Struct Mol Biol. 27:1–2. 2020. View Article : Google Scholar : PubMed/NCBI

15 

Suzuki T, Sassa A, Gruz P, Gupta RC, Johnson F, Adachi N and Nohmi T: Error-prone bypass patch by a low-fidelity variant of DNA polymerase zeta in human cells. DNA Repair (Amst). 100:1030522021. View Article : Google Scholar : PubMed/NCBI

16 

Gaczynska M and Osmulski PA: Targeting protein-protein interactions in the ubiquitin-proteasome pathway. Adv Protein Chem Struct Biol. 110:123–165. 2018. View Article : Google Scholar : PubMed/NCBI

17 

Bi W, Zhu L, Zeng Z, Jing X, Liang Y, Guo L, Shi Q, Xu A and Tao E: Investigations into the role of 26S proteasome non-ATPase regulatory subunit 13 in neuroinflammation. Neuroimmunomodulation. 21:331–337. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Bard JAM, Goodall EA, Greene ER, Jonsson E, Dong KC and Martin A: Structure and function of the 26S proteasome. Ann Rev Biochem. 87:697–724. 2018. View Article : Google Scholar : PubMed/NCBI

19 

Chen X, Htet ZM, Lopez-Alfonzo E, Martin A and Walters KJ: Proteasome interaction with ubiquitinated substrates: From mechanisms to therapies. FEBS J. Nov 19–2020.(Epub ahead of print). View Article : Google Scholar

20 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Tu Y, Chen C, Pan J, Xu J, Zhou ZG and Wang CY: The Ubiquitin Proteasome Pathway (UPP) in the regulation of cell cycle control and DNA damage repair and its implication in tumorigenesis. Int J Clin Exp Pathol. 5:726–738. 2012.PubMed/NCBI

22 

Sakai W, Yuasa-Sunagawa M, Kusakabe M, Kishimoto A, Matsui T, Kaneko Y, Akagi JI, Huyghe N, Ikura M, Ikura T, et al: Functional impacts of the ubiquitin-proteasome system on DNA damage recognition in global genome nucleotide excision repair. Sci Rep. 10:197042020. View Article : Google Scholar : PubMed/NCBI

23 

Ramadan K and Meerang M: Degradation-linked ubiquitin signal and proteasome are integral components of DNA double strand break repair: New perspectives for anti-cancer therapy. FEBS Lett. 585:2868–2875. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Rizzo AA, Vassel FM, Chatterjee N, D'Souza S, Li Y, Hao B, Hemann MT, Walker GC and Korzhnev DM: Rev7 dimerization is important for assembly and function of the Rev1/Polζ translesion synthesis complex. Proc Natl Acad Sci USA. 115:E8191–E8200. 2018. View Article : Google Scholar : PubMed/NCBI

25 

Feng L, Wei W, Heng Z, Yantao H and Chunbo W: Knockdown of REV7 inhibits breast cancer cell migration and invasion. Oncol Res. 24:315–325. 2016. View Article : Google Scholar : PubMed/NCBI

26 

Rosenberg SC and Corbett KD: The multifaceted roles of the HORMA domain in cellular signaling. J Cell Biol. 211:745–755. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Hara K, Taharazako S, Ikeda M, Fujita H, Mikami Y, Kikuchi S, Hishiki A, Yokoyama H, Ishikawa Y, Kanno SI, et al: Dynamic feature of mitotic arrest deficient 2-like protein 2 (MAD2L2) and structural basis for its interaction with chromosome alignment-maintaining phosphoprotein (CAMP). J Biol Chem. 292:17658–17667. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Sanders MA, Haynes B, Nangia-Makker P, Polin LA and Shekhar MP: Pharmacological targeting of RAD6 enzyme-mediated translesion synthesis overcomes resistance to platinum-based drugs. J Biol Chemistry. 292:10347–10363. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Jantrapirom S, Piccolo LL, Pruksakorn D, Potikanond S and Nimlamool W: Ubiquilin networking in cancers. Cancers. 12:1206–1586. 2020. View Article : Google Scholar : PubMed/NCBI

30 

Leestemaker Y and Ovaa H: Tools to investigate the ubiquitin proteasome system. Drug discovery today. Technologies. 26:25–31. 2017.PubMed/NCBI

31 

Wehmer M, Rudack T, Beck F, Aufderheide A, Pfeifer G, Plitzko JM, Förster F, Schulten K, Baumeister W and Sakata E: Structural insights into the functional cycle of the ATPase module of the 26S proteasome. Proc Natl Acad Sci USA. 114:1305–1310. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Rizzo AA and Korzhnev DM: The Rev1-Polζ translesion synthesis mutasome: Structure, interactions and inhibition. Enzymes. 45:139–181. 2019. View Article : Google Scholar : PubMed/NCBI

33 

Fernandes E, Fonseca TG, Carriço T, Mestre N, Tavares Á and Bebianno MJ: Cytotoxic responses of the anticancer drug cyclophosphamide in the mussel Mytilus galloprovincialis and comparative sensitivity with human cells lines. Chemosphere. 261:1276782020. View Article : Google Scholar : PubMed/NCBI

34 

Kanao R and Masutani C: Regulation of DNA damage tolerance in mammalian cells by post-translational modifications of PCNA. Mutat Res. 803-805:82–88. 2017. View Article : Google Scholar : PubMed/NCBI

35 

Lau WCY, Li Y, Zhang Q and Huen MSY: Molecular architecture of the Ub-PCNA/Pol η complex bound to DNA. Sci Rep. 5:157592015. View Article : Google Scholar : PubMed/NCBI

36 

Quinet A, Lerner LK, Martins DJ and Menck CFM: Filling gaps in translesion DNA synthesis in human cells. Mutat Res Genet Toxicol Environ Mutagen. 836:127–142. 2018. View Article : Google Scholar : PubMed/NCBI

37 

An H, Yang L, Wang C, Gan Z, Gu H, Zhang T, Huang X, Liu Y, Li Y, Chang SJ, et al: Interactome analysis reveals a novel role for RAD6 in the regulation of proteasome activity and localization in response to DNA damage. Mol Cell Biol. 37:e00419–e00416. 2017. View Article : Google Scholar

38 

Masuda Y and Masutani C: Spatiotemporal regulation of PCNA ubiquitination in damage tolerance pathways. Crit Rev Biochem Mol Biol. 54:418–442. 2019. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ma L, Li X, Zhao X, Sun H, Kong F, Li Y, Sui Y and Xu F: Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells. Mol Med Rep 24: 629, 2021.
APA
Ma, L., Li, X., Zhao, X., Sun, H., Kong, F., Li, Y. ... Xu, F. (2021). Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells. Molecular Medicine Reports, 24, 629. https://doi.org/10.3892/mmr.2021.12268
MLA
Ma, L., Li, X., Zhao, X., Sun, H., Kong, F., Li, Y., Sui, Y., Xu, F."Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells". Molecular Medicine Reports 24.3 (2021): 629.
Chicago
Ma, L., Li, X., Zhao, X., Sun, H., Kong, F., Li, Y., Sui, Y., Xu, F."Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells". Molecular Medicine Reports 24, no. 3 (2021): 629. https://doi.org/10.3892/mmr.2021.12268
Copy and paste a formatted citation
x
Spandidos Publications style
Ma L, Li X, Zhao X, Sun H, Kong F, Li Y, Sui Y and Xu F: Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells. Mol Med Rep 24: 629, 2021.
APA
Ma, L., Li, X., Zhao, X., Sun, H., Kong, F., Li, Y. ... Xu, F. (2021). Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells. Molecular Medicine Reports, 24, 629. https://doi.org/10.3892/mmr.2021.12268
MLA
Ma, L., Li, X., Zhao, X., Sun, H., Kong, F., Li, Y., Sui, Y., Xu, F."Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells". Molecular Medicine Reports 24.3 (2021): 629.
Chicago
Ma, L., Li, X., Zhao, X., Sun, H., Kong, F., Li, Y., Sui, Y., Xu, F."Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells". Molecular Medicine Reports 24, no. 3 (2021): 629. https://doi.org/10.3892/mmr.2021.12268
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