Expression and Clinical Significance of the Endoplasmic Reticulum PERK/eIF-2α Signaling Pathway in Cervical Cancer

Peipei HE; Ke CHEN; Jun XU; Zhixia WANG; Xuemei YAN

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Peipei HE, Ke CHEN, Jun XU, Zhixia WANG, Xuemei YAN. Expression and Clinical Significance of the Endoplasmic Reticulum PERK/eIF-2α Signaling Pathway in Cervical Cancer[J]. Journal of Kunming Medical University.

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Peipei HE, Ke CHEN, Jun XU, Zhixia WANG, Xuemei YAN. Expression and Clinical Significance of the Endoplasmic Reticulum PERK/eIF-2α Signaling Pathway in Cervical Cancer[J]. Journal of Kunming Medical University.

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Expression and Clinical Significance of the Endoplasmic Reticulum PERK/eIF-2α Signaling Pathway in Cervical Cancer

Department of Gynecology，Nanjing Mingji Hospital /Benji Hospital Affiliated toNanjing Medical University，Nanjing Jiangsu 210000，China

Received Date: 2025-07-14

Abstract

Abstract

Objective : To investigate the expression of the endoplasmic reticulum stress protein kinase R-like endoplasmic reticulum kinase （PERK）/eukaryotic initiation factor 2α （eIF-2α） signaling pathway in cervical intraepithelial neoplasia （CIN） and cervical carcinoma （CC）, and its impact on tumor progression. Methods: Biopsy specimens from 29 CC patients were collected as the CC group, 26 cases of cervical intraepithelial neoplasia （CIN II and CIN III） served as the control group, and cervical tissues from 17 healthy uterine patients constituted the normal group. Western blot was used to detect the expression of endoplasmic reticulum-mediated related proteins; immunohistochemistry was employed to assess the staining status of PERK/eIF-2α in CC tissues. HeLa cells were divided into the following groups: control group, pcDNA3.1-NC group, overexpressed PERK group, sh-NC group, and PERK interference group. Cell proliferation activity was detected using the CCK-8 assay, and the expression of epithelial cadherin （E-cadherin） was observed by immunofluorescence staining. Apoptosis and cell cycle distribution were analyzed by flow cytometry, and cell migration and invasion ability were evaluated by Transwell assay. Results With increasing CIN grade, the expression of PERK/eIF-2α increased （P < 0.05）, and its expression in CC tissues was significantly higher than that in CIN tissues （P < 0.05）. Compared with the pcDNA3.1-NC group, cells in the PERK overexpression group enhanced proliferation activity, markedly reduced intracellular E-cadherin fluorescence expression （P < 0.05）, and downregulated E-cadherin protein expression （P < 0.05）, accompanied by promotion of cell proliferation, migration, and invasion, as well as inhibition of apoptosis （P < 0.05）. In contrast, compared with the sh-NC group, cells in the PERK interference group showed decreased proliferation activity, significantly increased intracellular E-cadherin fluorescence expression （P < 0.05）, upregulated E-cadherin protein expression （P < 0.05）, along with inhibition of cell proliferation, migration, and invasion, and promotion of apoptosis （P < 0.05）. Conclusion The expression of the endoplasmic reticulum stress-related PERK/eIF-2α pathway is upregulated in uterine intraepithelial neoplasia and CC tissues. Inhibition of its expression can reduce the tumor cell proliferation in CC, thereby slowing tumor progression.
- Cervical cancer,
- Endoplasmic reticulum stress,
- Protein kinase R-like endoplasmic reticulum kinase,
- Eukaryotic initiation factor 2α

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References(23)

References

[1]	Buskwofie A, David-West G, Clare C A. A review of cervical cancer: Incidence and disparities[J]. J Natl Med Assoc, 2020, 112(2): 229-232.
[2]	Bertone F, Serusi E, Liscia D S, et al. Thyroid gland metastasis from endometrial carcinoma causing acute severe dyspnea[J]. Ear Nose Throat J, 2024, 103(3): NP142-NP144. doi: 10.1177/01455613211045564
[3]	徐海花, 孙蓬明. Toll 样受体与输卵管疾病[J]. 中国生育健康杂志, 2020, 31(3): 289-291.
[4]	李海英, 蔡竞, 朱虹丽. 宫颈癌的临床治疗研究进展[J]. 宁夏医科大学学报, 2020, 42(4): 419-422. doi: 10.19844/j.cnki.1672-397X.2024.11.020
[5]	李洵, 付晓霞, 樊丽伟, 等. 乔松素抑制人胃癌细胞系 AGS 增殖、迁移和侵袭的研究[J]. 基础医学与临床, 2022, 42(11): 1744-1749. doi: 10.16352/j.issn.1001-6325.2022.11.1744
[6]	李聪聪, 赵鹏, 秦燕勤, 等. 淫羊藿苷的药理活性研究进展[J]. 中医学报, 2020, 35: 781-786. doi: 10.16368/j.issn.1674-8999.2020.04.175
[7]	Chen H, Chen G M, Liu Y J, et al. Alpha-fetoprotein/endoplasmic reticulum stress signaling mitigates injury in hepatoma cells[J]. Neoplasma, 2021, 68(5): 983-993. doi: 10.4149/neo_2021_210205n180
[8]	Izadpanah A, Willingham K, Chandrasekar B, et al. Unfolded protein response and angiogenesis in malignancies[J]. Biochim Biophys Acta BBA Rev Cancer, 2023, 1878(2): 188839. doi: 10.1016/j.bbcan.2022.188839
[9]	Kumar A, Kumar N, Pathak Z, et al. Extra cellular matrix remodeling: An adjunctive target for spinal cord injury and intervertebral disc degeneration[J]. Neurospine, 2022, 19(3): 632-645. doi: 10.14245/ns.2244366.183
[10]	Oakes S A. Endoplasmic reticulum stress signaling in cancer cells[J]. Am J Pathol, 2020, 190(5): 934-946. doi: 10.1016/j.ajpath.2020.01.010
[11]	Lemmer I L, Willemsen N, Hilal N, et al. A guide to understanding endoplasmic reticulum stress in metabolic disorders[J]. Mol Metab, 2021, 47: 101169. doi: 10.1016/j.molmet.2021.101169
[12]	周琦, 吴小华, 刘继红, 等. 宫颈癌诊断与治疗指南(第四版)[J]. 中国实用妇科与产科杂志, 2018, 34(6): 613-622.
[13]	中华医学会妇科肿瘤学分会. 中国宫颈癌及癌前病变诊疗指南(2022年版)[J]. 中华妇产科杂志, 2022, 57(4): 256-269.
[14]	Magaki S, Hojat S A, Wei B, et al. An introduction to the performance of immunohistochemistry[J]. Methods Mol Biol, 2019, 1897: 289-298.
[15]	Hernandez I, Cohen M. Linking cell-surface GRP78 to cancer: From basic research to clinical value of GRP78 antibodies[J]. Cancer Lett, 2022, 524: 1-14. doi: 10.1016/j.canlet.2021.10.004
[16]	Khan M, Sharma A, Hathorn T, et al. The mucosal manifestations of syphilis in the head and neck[J]. Ear Nose Throat J, 2025, 104(12): NP868-NP881.
[17]	Dhara V, Hoda N, Rajini B C, et al. Significance of cervical node necrosis in preoperative MRI as a prognostic indicator: Retrospective study of patients with SCC of tongue[J]. J Oral Med Oral Surg, 2021, 27(3): 43. doi: 10.1051/mbcb/2021021
[18]	刘红, 王增四, 高文, 等. 黄芪甲苷对 STZ 诱导糖尿病大鼠肾组织内质网应激及 CHOP 信号通路的影响[J]. 中国医院药学杂志, 2021, 41(13): 1318-1323. doi: 10.13286/j.1001-5213.2021.13.08
[19]	Yoo Y M, Joo S S. Melatonin can modulate neurodegenerative diseases by regulating endoplasmic reticulum stress[J]. Int J Mol Sci, 2023, 24(3): 2381. doi: 10.3390/ijms24032381
[20]	林善婷, 胡晓, 李来好, 等. 水产蛋白源生物活性肽研究进展[J]. 大连海洋大学学报, 2020, 35: 775-785. doi: 10.16535/j.cnki.dlhyxb.2019-266
[21]	练毅, 宫丽荣, 余剑波, 等. 内质网应激介导的细胞凋亡与急性肺损伤的研究进展[J]. 中国中西医结合外科杂志, 2021, 27(2): 3. doi: 10.3969/j.issn.1007-6948.2021.02.039
[22]	童凯, 罗红兰. 洛铂通过PERK/eIF2α/ATF4/CHOP信号通路调节肺癌细胞A549的作用机制[J]. 世界临床药物, 2023, 44(8): 805. doi: 10.13683/j.wph.2023.08.007
[23]	张超云, 费娜, 郝鹏飞, 等. 基于内质网应激探讨葛根芩连汤对非酒精性脂肪肝大鼠PERK-eIF2α通路的影响[J]. 中国医院药学杂志, 2024, 44(4): 384-390. doi: 10.13286/j.1001-5213.2024.04.04

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