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Original Research

Open Access

APOBEC3G inhibits apoptosis and autophagy in cervical intraepithelial neoplasia W12 cells

  • Yanru Lin1
  • Zhuo Zhang2
  • Jiating Guo3
  • Lin Sun4,*,

1Department of Obstetrics and Gynecology, Beihua University Affiliated Hospital, 132001 Jilin, Jilin, China

2Department of Obstetrics and Gynecology, Liaoyuan City Fuying Hospital, 136201 Liaoyuan, Jilin, China

3Department of Internal Medicine, Community Health Service Center of Yunshan Street, 136201 Liaoyuan, Jilin, China

4Department of Endocrine, Sanya People’s Hospital, 572000 Sanya, Hainan, China

DOI: 10.22514/ejgo.2024.101 Vol.45,Issue 5,October 2024 pp.140-145

Submitted: 18 April 2024 Accepted: 26 June 2024

Published: 15 October 2024

*Corresponding Author(s): Lin Sun E-mail: sunlin2508@163.com

Abstract

Cervical intraepithelial neoplasia (CIN) is a collective term for specific precancerous lesions associated with cervical cancer (CC). Given the current poor prognosis, it is imperative to diagnose CIN at an early stage and identify the markers linked to its pathogenesis and prognosis, despite the disease’s documented slow course and numerous levels of cellular alterations. We explored the expression level of the new marker apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G, A3G) and its regulatory effect on CIN. Cell proliferation were assessed using Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) staining. Apoptosis rate was detected by flow cytometry. We used immunofluorescence to determine light chain 3B (LC3B) expression. Western blotting was used to detect Bcl2-Associated X (Bax), B-cell lymphoma 2 (Bcl-2), Cleaved caspase-3, p62, LC3-II/LC3-I, transforming growth factor-beta (TGF-β) and decapentaplegic homolog 2 (Smad2) expressions. A3G knockdown significantly inhibited cervical intraepithelial neoplasia cell proliferation, significantly increasing the apoptosis rate and the Bax/Bcl-2 ratio. Also, Cleaved-caspase-3 and LC-II expressions were significantly increased, and p62 expression was decreased. The TGF-β/Smad2 signaling pathway was significantly inhibited. In cervical intraepithelial neoplasia, APOBEC3G inhibits apoptosis and autophagy of W12 cells through TGFβ/Smad2 signaling pathway. In conclusion, we determined that APOBEC3G has a regulatory effect on CIN, which opens a new way to explore its pathogenesis and improve the accuracy of prognosis.


Keywords

Cervical intraepithelial neoplasia; APOBEC3G; Autophagy; Apoptosis; TGF-β/Smad2


Cite and Share

Yanru Lin,Zhuo Zhang,Jiating Guo,Lin Sun. APOBEC3G inhibits apoptosis and autophagy in cervical intraepithelial neoplasia W12 cells. European Journal of Gynaecological Oncology. 2024. 45(5);140-145.

References

[1] Bowden SJ, Doulgeraki T, Bouras E, Markozannes G, Athanasiou A, Grout-Smith H, et al. Risk factors for human papillomavirus infection, cervical intraepithelial neoplasia and cervical cancer: an umbrella review and follow-up Mendelian randomisation studies. BMC Medicine. 2023; 21: 274.

[2] Kremer WW, Steenbergen R, Heideman D, Kenter GG, Meijer C. The use of host cell DNA methylation analysis in the detection and management of women with advanced cervical intraepithelial neoplasia: a review. An International Journal of Obstetrics & Gynaecology. 2021; 128: 504–514.

[3] Loopik DL, Bentley HA, Eijgenraam MN, IntHout J, Bekkers RLM, Bentley JR. The natural history of cervical intraepithelial neoplasia grades 1, 2, and 3: a systematic review and meta-analysis. Journal of Lower Genital Tract Disease. 2021; 25: 221–231.

[4] Liu H, Liang H, Li D, Wang M, Li Y. Association of cervical dysbacteriosis, HPV oncogene expression, and cervical lesion progression. Microbiology Spectrum. 2022; 10: e0015122.

[5] Zhu Q, Zhang G, Tang M, Wu L. Expression and analysis of Rsf-1 and P16 in cervical intraepithelial neoplasia. European Journal of Gynaecological Oncology. 2022; 43: 271–277.

[6] Li Y, Langley CA, Azumaya CM, Echeverria I, Chesarino NM, Emerman M, et al. The structural basis for HIV-1 Vif antagonism of human APOBEC3G. Nature. 2023; 615: 728–733.

[7] Yang H, Kim K, Li S, Pacheco J, Chen XS. Structural basis of sequence-specific RNA recognition by the antiviral factor APOBEC3G. Nature Communications. 2022; 13: 7498.

[8] Vartanian J, Guétard D, Henry M, Wain-Hobson S. Evidence for editing of human papillomavirus DNA by APOBEC3 in benign and precancerous lesions. Science. 2008; 320: 230–233.

[9] Schmitt K, Guo K, Algaier M, Ruiz A, Cheng F, Qiu J, et al. Differential virus restriction patterns of rhesus macaque and human APOBEC3A: implications for lentivirus evolution. Virology. 2011; 419: 24–42.

[10] Chen S, Li X, Qin J, Chen Y, Liu L, Zhang D, et al. APOBEC3A possesses anticancer and antiviral effects by differential inhibition of HPV E6 and E7 expression on cervical cancer. International Journal of Clinical and Experimental Medicine. 2015; 8: 10548–10557.

[11] Iizuka T, Wakae K, Nakamura M, Kitamura K, Ono M, Fujiwara H, et al. APOBEC3G is increasingly expressed on the human uterine cervical intraepithelial neoplasia along with disease progression. American Journal of Reproductive Immunology. 2017; 78.

[12] Wang Y, Wu S, Zheng S, Wang S, Wali A, Ezhilarasan R, et al. APOBEC3G acts as a therapeutic target in mesenchymal gliomas by sensitizing cells to radiation-induced cell death. Oncotarget. 2017; 8: 54285–54296.

[13] Valera M, de Armas-Rillo L, Barroso-González J, Ziglio S, Batisse J, Dubois N, et al. The HDAC6/APOBEC3G complex regulates HIV-1 infectiveness by inducing Vif autophagic degradation. Retrovirology. 2015; 12: 53.

[14] Han Y, Li Q, Ling C, Jin M, Li D, Zhong J, et al. HPV-induced MiR-21 promotes epithelial mesenchymal transformation and tumor progression in cervical cancer cells through the TGFβ R2/hTERC pathway. Contrast Media & Molecular Imaging. 2022: 2022: 6297694.

[15] Chaffer CL, Brennan JP, Slavin JL, Blick T, Thompson EW, Williams ED. Mesenchymal-to-epithelial transition facilitates bladder cancer metastasis: role of fibroblast growth factor receptor-2. Cancer Research. 2006; 66: 11271–11278.

[16] Lee TK, Poon RTP, Yuen AP, Ling MT, Kwok WK, Wang XH, et al. Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition. Clinical Cancer Research. 2006; 12: 5369–5376.

[17] Kusakabe M, Taguchi A, Sone K, Mori M, Osuga Y. Carcinogenesis and management of human papillomavirus-associated cervical cancer. International Journal of Clinical Oncology. 2023; 28: 965–974.

[18] Perkins RB, Wentzensen N, Guido RS, Schiffman M. Cervical cancer screening. JAMA. 2023; 330: 547.

[19] Antonioli M, Pagni B, Vescovo T, Ellis R, Cosway B, Rollo F, et al. HPV sensitizes OPSCC cells to cisplatin-induced apoptosis by inhibiting autophagy through E7-mediated degradation of AMBRA1. Autophagy. 2021; 17: 2842–2855.

[20] Wu X, Xiao Y, Guo D, Zhang Z, Liu M. Reduced NK cell cytotoxicity by papillomatosis-derived TGF-β contributing to low-risk HPV persistence in JORRP patients. Frontiers in Immunology. 2022; 13: 849493.

[21] Tong Y, Kikuhara S, Onodera T, Chen L, Myat AB, Imamichi S, et al. Radiosensitization to γ-ray by functional inhibition of APOBEC3G. International Journal of Molecular Sciences. 2022; 23: 5069.

[22] Cao W, Li J, Yang K, Cao D. An overview of autophagy: Mechanism, regulation and research progress. Bulletin du Cancer. 2021; 108: 304–322.

[23] Miller DR, Thorburn A. Autophagy and organelle homeostasis in cancer. Developmental Cell. 2021; 56: 906–918.

[24] Peña-Martinez C, Rickman AD, Heckmann BL. Beyond autophagy: LC3-associated phagocytosis and endocytosis. Science Advances. 2022; 8: eabn1702.

[25] Marino-Merlo F, Klett A, Papaianni E, Drago SFA, Macchi B, Rincón MG, et al. Caspase-8 is required for HSV-1-induced apoptosis and promotes effective viral particle release via autophagy inhibition. Cell Death & Differentiation. 2023; 30: 885–896.

[26] Xue Q, Kang R, Klionsky DJ, Tang D, Liu J, Chen X. Copper metabolism in cell death and autophagy. Autophagy. 2023; 19: 2175–2195.

[27] Peng D, Fu M, Wang M, Wei Y, Wei X. Targeting TGF-β signal transduction for fibrosis and cancer therapy. Molecular Cancer. 2022; 21: 104.

[28] MaruYama T, Chen W, Shibata H. TGF-β and cancer immunotherapy. Biological and Pharmaceutical Bulletin. 2022; 45: 155–161.


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