Shen X.a· Li L.b· He Y.b· Lv X.b· Ma J.b

Author affiliations

aDepartment of Gastrointestinal Surgery, Xi’an Daxing Hospital, Xi’an, China
bDepartment of Obstetrics & Gynecology, Fourth Military Medical University, Xi’an, China

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Article / Publication Details

First-Page Preview

Received: September 08, 2021
Accepted: March 08, 2022
Published online: May 31, 2022

Number of Print Pages: 10
Number of Figures: 4
Number of Tables: 0

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: https://www.karger.com/PHA

Abstract

Introduction: Cervical cancer is a severe malignant tumor that endangers the health of women worldwide. Eukaryotic initiation factor-5A2 (EIF5A2) expression has been reported to be increased in cervical cancer and correlates with prognosis. An attempt was made in this paper to explore the impact and potential mechanisms of EIF5A2 in the cell biology of cervical cancer. Methods: We first knocked down EIF5A2 in cervical cancer cells. Then, we examined the proliferation, migration, invasion, and apoptosis of these cells by cell counting kit 8, wound healing, Transwell, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays. Cells were processed with different concentrations of cisplatin to observe their sensitivity to cisplatin. Next, the relationship between EIF5A2 and anterior gradient 2 (AGR2) was verified by co-immunoprecipitation. Following AGR2 overexpression, the biological processes of these cells were examined. Results: EIF5A2 knockdown inhibited cell proliferation, migration, and invasion, and it promoted apoptosis and enhanced the sensitivity to cisplatin in cervical cancer cells. Additionally, AGR2 expression was positively correlated with EIF5A2, and its overexpression alleviated the reduction in proliferation, migration, and invasion of cervical cancer cells induced by EIF5A2 knockdown. Overexpression of AGR2 also reduced apoptosis and their sensitivity to cisplatin in EIF5A2-knockdwon cervical cancer cells. Conclusion: EIF5A2 knockdown inhibited the biological process of cervical cancer cells through modulation of AGR2. The in-depth investigation of the molecular mechanism of EIF5A2 in cervical cancer cells provides new strategies for the prevention and treatment of clinical malignancies.

© 2022 S. Karger AG, Basel

References Ji N, Wang Y, Bao G, Yan J, Ji S. LncRNA SNHG14 promotes the progression of cervical cancer by regulating miR-206/YWHAZ. Pathol Res Pract. 2019 Apr;215(4):668–75. Moela P, Motadi LR. RBBP6: a potential biomarker of apoptosis induction in human cervical cancer cell lines. Onco Targets Ther. 2016;9:4721–35. Gardner AB, Charo LM, Mann AK, Kapp DS, Eskander RN, Chan JK. Ovarian, uterine, and cervical cancer patients with distant metastases at diagnosis: most common locations and outcomes. Clin Exp Metastasis. 2020 Feb;37(1):107–13. Calys-Tagoe BNL, Aheto JMK, Mensah G, Biritwum RB, Yawson AE. Cervical cancer screening practices among women in Ghana: evidence from wave 2 of the WHO study on global AGEing and adult health. BMC Womens Health. 2020 Mar 5;20(1):49. You KY, Peng HH, Jiang YH, Bi ZF, Qiu XS. Selective use of concurrent chemotherapy in elderly cervical cancer patients treated with definitive radiotherapy: experience from two institutions. Cancer Manag Res. 2019;11:4815–23. Zhao G, Zhang W, Dong P, Watari H, Guo Y, Pfeffer LM, et al. EIF5A2 controls ovarian tumor growth and metastasis by promoting epithelial to mesenchymal transition via the TGFbeta pathway. Cell Biosci. 2021 Apr 7;11(1):70. Liu Y, Du F, Chen W, Yao M, Lv K, Fu P. EIF5A2 is a novel chemoresistance gene in breast cancer. Breast Cancer. 2015 Nov;22(6):602–7. Wang K, Wang Y, Wang Y, Liu S, Wang C, Zhang S, et al. EIF5A2 enhances stemness of epithelial ovarian cancer cells via a E2F1/KLF4 axis. Stem Cell Res Ther. 2021 Mar 16;12(1):186. Wei JH, Cao JZ, Zhang D, Liao B, Zhong WM, Lu J, et al. EIF5A2 predicts outcome in localised invasive bladder cancer and promotes bladder cancer cell aggressiveness in vitro and in vivo. Br J Cancer. 2014 Apr 2;110(7):1767–77. Yang SS, Gao Y, Wang DY, Xia BR, Liu YD, Qin Y, et al. Overexpression of eukaryotic initiation factor 5A2 (EIF5A2) is associated with cancer progression and poor prognosis in patients with early-stage cervical cancer. Histopathology. 2016 Aug;69(2):276–87. Moidu NA, A Rahman NS, Syafruddin SE, Low TY, Mohtar MA. Secretion of pro-oncogenic AGR2 protein in cancer. Heliyon. 2020 Sep 23;6(9):e05000. Liu R, Qian M, Zhou T, Cui P. TP53 mediated miR-3647-5p prevents progression of cervical carcinoma by targeting AGR2. Cancer Med. 2019 Oct;8(13):6095–105. Wang FW, Cai MY, Mai SJ, Chen JW, Bai HY, Li Y, et al. Ablation of EIF5A2 induces tumor vasculature remodeling and improves tumor response to chemotherapy via regulation of matrix metalloproteinase 2 expression. Oncotarget. 2014 Aug 30;5(16):6716–33. Hao F, Zhu Q, Lu L, Sun S, Huang Y, Zhang J, et al. EIF5A2 is highly expressed in anaplastic thyroid carcinoma and is associated with tumor growth by modulating TGF-signals. Oncol Res. 2020 Sep 1;28(4):345–55. Dong JS, Wu B, Zha ZL. MicroRNA-588 regulates migration capacity and invasiveness of renal cancer cells by targeting EIF5A2. Eur Rev Med Pharmacol Sci. 2019 Dec;23(23):10248–56. Li Y, Fu L, Li JB, Qin Y, Zeng TT, Zhou J, et al. Increased expression of EIF5A2, via hypoxia or gene amplification, contributes to metastasis and angiogenesis of esophageal squamous cell carcinoma. Gastroenterology. 2014 Jun;146(7):1701–13.e9. Yang H, Li XD, Zhou Y, Ban X, Zeng TT, Li L, et al. Stemness and chemotherapeutic drug resistance induced by EIF5A2 overexpression in esophageal squamous cell carcinoma. Oncotarget. 2015 Sep 22;6(28):26079–89. Chen C, Zhang B, Wu S, Song Y, Li J. Knockdown of EIF5A2 inhibits the malignant potential of non-small cell lung cancer cells. Oncol Lett. 2018 Apr;15(4):4541–9. Sun J, Xu Z, Lv H, Wang Y, Wang L, Ni Y, et al. eIF5A2 regulates the resistance of gastric cancer cells to cisplatin via induction of EMT. Am J Transl Res. 2018;10(12):4269–79. Lin YM, Chen ML, Chen CL, Yeh CM, Sung WW. Overexpression of EIF5A2 predicts poor prognosis in patients with oral squamous cell carcinoma. Diagnostics. 2020 Jun 27;10(7):436. Zhang Y, Zheng A, Xu R, Zhou F, Hao A, Yang H, et al. NR2F1-induced NR2F1-AS1 promotes esophageal squamous cell carcinoma progression via activating Hedgehog signaling pathway. Biochem Biophys Res Commun. 2019 Nov 12;519(3):497–504. Bai M, Wu ZZ, Huang YL, Ke J, Xu Q, Wang X. STAT3 activates the transcription of lncRNA NR2F1-AS1 to promote the progression of melanoma via regulating the miR-493-5p/GOLM1 axis. J Gene Med. 2021 Apr 6;23(7):e3338. Liang HX, Li YH. MiR-873, as a suppressor in cervical cancer, inhibits cells proliferation, invasion and migration via negatively regulating ULBP2. Genes Genomics. 2020 Apr;42(4):371–82. Mendez LC, Moraes FY, Castilho MS, Louie AV, Qu XM. Lives and economic loss in Brazil due to lack of radiotherapy access in cervical cancer: a cost-effectiveness analysis. Clin Oncol. 2019 Sep;31(9):e143–e48. Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM. Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol. 2000 Mar;18(5):1135–49. Jafarian AH, Vazife Mostaan L, Mohammadian Roshan N, Khazaeni K, Parsazad S, Gilan H. Relationship between the expression of matrix metalloproteinase and clinicopathologic features in oral squamous cell carcinoma. Iran J Otorhinolaryngol. 2015 May;27(80):219–23. Wang SS, Zheng M, Pang X, Zhang M, Yu XH, Wu JB, et al. Macrophage migration inhibitory factor promotes the invasion and metastasis of oral squamous cell carcinoma through matrix metalloprotein-2/9. Mol Carcinog. 2019 Oct;58(10):1809–21. Chen YT, Ho CL, Chen PK, Chen YL, Chang CF. Anterior gradient 2: a novel sensitive tumor marker for metastatic oral cancer. Cancer Lett. 2013 Oct 10;339(2):270–8. Zhang JS, Gong A, Cheville JC, Smith DI, Young CY. AGR2, an androgen-inducible secretory protein overexpressed in prostate cancer. Genes Chromosomes Cancer. 2005 Jul;43(3):249–59. Innes HE, Liu D, Barraclough R, Davies MP, O’Neill PA, Platt-Higgins A, et al. Significance of the metastasis-inducing protein AGR2 for outcome in hormonally treated breast cancer patients. Br J Cancer. 2006 Apr 10;94(7):1057–65. Riener MO, Pilarsky C, Gerhardt J, Grutzmann R, Fritzsche FR, Bahra M, et al. Prognostic significance of AGR2 in pancreatic ductal adenocarcinoma. Histol Histopathol. 2009 Sep;24(9):1121–8. Edgell TA, Barraclough DL, Rajic A, Dhulia J, Lewis KJ, Armes JE, et al. Increased plasma concentrations of anterior gradient 2 protein are positively associated with ovarian cancer. Clin Sci. 2010 Mar 30;118(12):717–25. Article / Publication Details

First-Page Preview

Received: September 08, 2021
Accepted: March 08, 2022
Published online: May 31, 2022

Number of Print Pages: 10
Number of Figures: 4
Number of Tables: 0

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: https://www.karger.com/PHA

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