Effect of the microRNA-874-3p/cytoplasmic polyadenylation element binding protein 4 signaling axis on the malignant biological behavior of cervical cancer cells

Fan Wenling; Qi Ziyu; Xing Jingna; Ren Yanan; Hao Shuwei

doi:10.13406/j.cnki.cyxb.004035

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Effect of the microRNA-874-3p/cytoplasmic polyadenylation element binding protein 4 signaling axis on the malignant biological behavior of cervical cancer cells

Precision medicine in cancer and translational studies | 更新时间：2026-10-26

- Effect of the microRNA-874-3p/cytoplasmic polyadenylation element binding protein 4 signaling axis on the malignant biological behavior of cervical cancer cells
- Journal of Chongqing Medical University Vol. 51, Issue 10, Pages: 1452-1461(2026)
- 作者机构：
  
  1.河北医科大学第四医院妇科，石家庄 050000
  2.河北医科大学研究生学院，石家庄 050017
  3.河北省第七人民医院妇科，定州 073000
  4.河北省人民医院妇科，石家庄 050057
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.004035
  CLC： R737.33
- Received：30 October 2025，
  
  Revised：2025-12-17，
  
  Accepted：05 January 2026，
  
  Published：28 October 2026
- 稿件说明：
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范文玲，齐子钰，邢景娜，等.miR-874-3p/CPEB4信号轴对宫颈癌细胞恶性生物学行为的影响[J].重庆医科大学学报，2026，51（10）：1452-1461.

Fan Wenling,Qi Ziyu,Xing Jingna,et al.Effect of the microRNA-874-3p/cytoplasmic polyadenylation element binding protein 4 signaling axis on the malignant biological behavior of cervical cancer cells[J].Journal of Chongqing Medical University,2026,51(10):1452-1461.
范文玲，齐子钰，邢景娜，等.miR-874-3p/CPEB4信号轴对宫颈癌细胞恶性生物学行为的影响[J].重庆医科大学学报，2026，51（10）：1452-1461. DOI： 10.13406/j.cnki.cyxb.004035.

Fan Wenling,Qi Ziyu,Xing Jingna,et al.Effect of the microRNA-874-3p/cytoplasmic polyadenylation element binding protein 4 signaling axis on the malignant biological behavior of cervical cancer cells[J].Journal of Chongqing Medical University,2026,51(10):1452-1461. DOI： 10.13406/j.cnki.cyxb.004035.

摘要

目的

探究长链非编码RNA（long non-coding ribonucleic acid，lncRNA）MCF2L-AS1调节微小RNA（micro ribonucleic acid，miR）-874-3p/胞质多聚腺苷酸化元件结合蛋白4（cytoplasmic polyadenylation element binding protein 4，CPEB4）信号轴对宫颈癌（cervical cancer，CC）细胞恶性生物学行为的影响。

方法

定量逆转录聚合酶链式反应（quantitative reverse transcription polymerase chain reaction，qRT-PCR）实验检测人正常宫颈上皮细胞（H8 cell line，H8）和CC细胞Hela、siha、HCC94中lncRNA MCF2L-AS1、miR-874-3p、CPEB4 mRNA表达水平；体外培养人CC细胞Hela，将其随机分成CC组（正常培养）、sh-NC组、sh-lncRNA MCF2L-AS1组、sh-lncRNA MCF2L-AS1+inhibitor-NC组、sh-lncRNA MCF2L-AS1+miR-874-3p inhibitor组。qRT-PCR实验检测各组Hela细胞lncRNA MCF2L-AS1、miR-874-3p、CPEB4 mRNA表达；双荧光素酶报告基因实验检测lncRNA MCF2L-AS1与miR-874-3p、miR-874-3p与CPEB4 mRNA之间的调控关系；平板克隆实验检测各组细胞增殖能力；划痕、Transwell和流式细胞仪实验检测各组细胞迁移、侵袭和凋亡能力；Western blot检测各组细胞增殖、迁移侵袭、凋亡、上皮间质转化（epithelial mesenchymal transition，EMT）、血管内皮生长因子（vascular endothelial growth factor，VEGF）及CPEB4蛋白表达。

结果

与H8细胞相比，Hela、siha、HCC94细胞中lncRNA MCF2L-AS1、CPEB4 mRNA表达升高（

0.05），miR-874-3p表达降低（

0.05），其中Hela变化最明显，以此为研究对象；sh-lncRNA MCF2L-AS1组Hela细胞lncRNA MCF2L-AS1、CPEB4 mRNA和蛋白、克隆数、迁移率、侵袭数量、Ki67、增殖细胞核抗原（proliferating cell nuclear antigen，PCNA）、基质金属蛋白酶9（matrix metallopeptidase 9，MMP-9）、N-cadherin、B淋巴细胞瘤-2（b-cell lymphoma-2，Bcl-2）、VEGF表达明显低于CC组、sh-NC组（

0.05），miR-874-3p、凋亡率、E-cadherin、BCL2相关X蛋白（bcl2 associated X protein，Bax）表达明显高于CC组、sh-NC组（

0.05）；sh-lncRNA MCF2L-AS1+miR-874-3p inhibitor组Hela细胞lncRNA MCF2L-AS1表达无明显变化，CPEB4 mRNA和蛋白、克隆数、迁移率、侵袭数量、Ki67、PCNA、MMP-9、N-cadherin、Bcl-2、VEGF表达明显高于sh-lncRNA MCF2L-AS1组、sh-lncRNA MCF2L-AS1+inhibitor-NC组（

0.05），miR-874-3p、凋亡率、E-cadherin、Bax表达明显低于sh-lncRNA MCF2L-AS1组、inhibitor-NC组（

0.05）。双荧光素酶报告基因实验结果显示，miR

-874-3p mimic组Hela细胞荧光素酶活性明显低于mimic-NC组。

结论

抑制lncRNA MCF2L-AS1表达通过上调miR-874-3p，进而减少CPEB4表达，明显抑制CC细胞恶性生物学行为。

Abstract

Objective

To investigate the effect of the long non-coding RNA（lncRNA） MCF2L-AS1 on the malignant biological behavior of cervical cancer（CC） cells by regulating the microRNA-874-3p（miR-874-3p）/cytoplasmic polyadenylation element binding protein 4（CPEB4） signaling axis.

Methods

The qRT-PCR experiment was used to measure the mRNA expression levels of lncRNA MCF2L-AS1，miR-874-3p，and CPEB4 mRNA in normal human cervical epithelial cells H8 and CC cell lines HeLa，siha，and HCC94. Human CC HeLa cells were cultured

in vitro

and were then randomly divided into CC group（normal culture），sh-NC group，sh-lncRNA MCF2L-AS1 group，sh-lncRNA MCF2L-AS1+inhibitor-NC group，and sh-lncRNA MCF2L-AS1+miR-874-3p inhibitor group. The qRT-PCR experiment was used to measure the mRNA expression levels of lncRNA MCF2L-AS1，miR-874-3p，and CPEB4 in HeLa cells； dual-luciferase reporter assay was used to investigate the regulatory relationship between lncRNA MCF2L-AS1 and miR-874-3p and between miR-874-3p and CPEB4； plate colony formation assay was used to observe the proliferative capacity of cells； scratch assay，Transwell assay，and flow cytometry were used to measure the migration，invasion，and apoptosis abilities of cells； Western blot was used to measure the expression levels of the proteins associated with cell proliferation，migration，invasion，apoptosis，and epithelial mesenchymal transition（EMT），as well as the protein expression levels of vascular endothelial growth factor（VEGF） and CPEB4.

Results

Compared with H8 cells，HeLa，siha，and HCC94 cells showed significant increases in the mRNA expression levels of lncRNA MCF2L-AS1 and CPEB4（

0.05） and a significant reduction in the expression level of miR-874-3p（

0.05），among which HeLa cells showed the greatest changes and were selected as the research object. Compared with the CC group and the sh-NC group，the sh-lncRNA MCF2L-AS1 group had significantly lower mRNA and protein expression levels of lncRNA MCF2L-AS1 and CPEB4 in HeLa cells，number of clones，migration rate，number of invasive cells，and expression levels of Ki67，proliferating cell nuclear antigen（PCNA），matrix metallopeptidase 9（MMP-9），N-cadherin，B-cell lymphoma-2（Bcl-2），and VEGF（

0.05），as well as significantly higher expression level of miR-874-3p，apoptosis rate，and expression levels of E-cadherin and Bcl-2 related X gene（Bax）（

0.05）. There was no significant change in the expression level of lncRNA MCF2L-AS1 in HeLa cells in the sh-lncRNA MCF2L-AS1+miR-874-3p inhibitor group，and compared with the sh-lncRNA MCF2L-AS1 group and the sh-lncRNA MCF2L-AS1+inhibitor-NC group，the sh-lncRNA MCF2L-AS1+miR-874-3p inhibitor group had significantly higher mRNA and protein expression levels of CPEB4，number of clones，migration rate，number of invasive cells，and expression levels of Ki67，PCNA，MMP-9，N-cadherin，Bcl-2，and VEGF（

0.05），as well as significantly lower expression level of miR-874-3p，apoptosis rate，and expression levels of E-cadherin and Bax（

0.05）. Dual-luciferase reporter assay showed that compared with the mimic-NC group，the miR-874-3p mimic group had a significantly lower luciferase activity of HeLa.

Conclusion

Inhibiting the expression of lncRNA MCF2L-AS1 can significantly inhibit the malignant biological behaviors of CC cells by upregulating the expression of miR-874-3p and reducing the expression of CPEB4.

关键词

Keywords

references

Revathidevi S ， Murugan AK ， Nakaoka H ， et al . APOBEC： A molecular driver in cervical cancer pathogenesis [J ] . Cancer Lett ， 2021 ， 496 ： 104 - 116 ．

Chen YF ， Shen M-R . The important role of ion transport system in cervical cancer [J ] . Int J Mol Sci ， 2022 ， 23 （ 1 ）： 333 ．

Gutiérrez-Hoya A ， Soto-Cruz I . NK cell regulation in cervical cancer and strategies for immunotherapy [J ] . Cells ， 2021 ， 10 （ 11 ）： 3104 ．

Huang FK ， Zheng CY ， Huang LK ， et al . Long non-coding RNA MCF2L-AS1 promotes the aggressiveness of colorectal cancer by sponging miR-874-3p and thereby up-regulating CCNE1 [J ] . J Gene Med ， 2021 ， 23 ： e3285 ．

Li SG ， Lin LC . Long non-coding RNA MCF2L-AS1promotes the cancer stem cell-like traits in non-small cell lung cancer cells through regulatingmiR-873-5p level [J ] . Environ Toxicol ， 2021 ， 36 （ 7 ）： 1457 - 1465 ．

Luo SD ， Tsai HT ， Hwang CF ， et al . Aberrant miR-874-3p/leptin/EGFR/c-Myc signaling contributes to nasopharyngeal carcinoma pathogenesis [J ] . J Exp Clin Cancer Res ， 2022 ， 41 （ 1 ）： 215 ．

Liu WG ， Zhuo L ， Lu Y ， et al . MiR-874-3p inhibits cell migration through targeting RGS4 in osteosarcoma [J ] . J Gene Med ， 2020 ， 22 （ 9 ）： e3213 ．

Zhang YQ ， Gan HY ， Zhao F ， et al . CPEB4-promoted paclitaxel resistance in ovarian cancer in vitro relies on translational regulation of CSAG2 [J ] . Front Pharmacol ， 2021 ， 11 ： 600994 ．

Delgado ME ， Naranjo-Suarez S ， Ramírez-Pedraza M ， et al . CPEB4 modulates liver cancer progression by translationally regulating hepcidin expression and sensitivity to ferroptosis [J ] . JHEP Rep ， 2025 ， 7 （ 3 ）： 101296 ．

Sibilio A ， Suñer C ， Fernández-Alfara M ， et al . Immune translational control by CPEB4 regulates intestinal inflammation resolution and colorectal cancer development [J ] . iScience ， 2022 ， 25 （ 2 ）： 103790 ．

Voelker RA . Cervical cancer screening [J ] . Jama ， 2023 ， 330 （ 20 ）： 2030 ．

Shen SN ， Zhang SB ， Liu P ， et al . Potential role of microRNAs in the treatment and diagnosis of cervical cancer [J ] . Cancer Genet ， 2020 ， 248/249 ： 25 - 30 ．

Aswathy R ， Sumathi S . Defining new biomarkers for overcoming therapeutical resistance in cervical cancer using lncRNA [J ] . Mol Biol Rep ， 2023 ， 50 （ 12 ）： 10445 - 10460 ．

Kong WC ， Li H ， Xie LS ， et al . LncRNA MCF2L-AS1 aggravates the malignant development of colorectal cancer via targeting miR-105-5p/RAB22A axis [J ] . BMC Cancer ， 2021 ， 21 （ 1 ）： 1069 ．

Ou HL ， Qian YS ， Ma L . MCF2L-AS1 promotes the biological behaviors of hepatocellular carcinoma cells by regulating the miR-33a-5p/FGF2 axis [J ] . Aging ， 2023 ， 15 （ 13 ）： 6100 - 6116 ．

王金礼，陈登峰 . 沉默lncRNA MCF2L-AS1通过miR-138-5p/AnxA2轴抑制乳腺癌细胞增殖、迁移和侵袭 [J ] . 现代肿瘤医学， 2024 ， 32 （ 2 ）： 240 - 248 .

Wang JL ， Chen DF . Silent lncRNA MCF2L-AS1 inhibits the proliferation，migration and invasion of breast cancer cells through the miR-138-5p/AnxA2 axis [J ] . Mod Oncol Med ， 2024 ， 32 （ 2 ）： 240 - 248 .

Liu JL ， Zhang J ， Hu Y ， et al . Inhibition of lncRNA DCST1-AS1 suppresses proliferation，migration and invasion of cervical cancer cells by increasing miR-874-3p expression [J ] . J Gene Med ， 2021 ， 23 ： e3281 ．

Li F ， Wei YY ， Chen T ， et al . Molecular network analysis of CPEB4 translational control and targeting CPEB4/β-catenin to modulate invasion and migration of nasopharyngeal carcinoma cells [J ] . Int J Med Sci ， 2025 ， 22 （ 6 ）： 1329 - 1343 ．

Li C ， Feng SY ， Chen L . MSC-AS1 knockdown inhibits cell growth and temozolomide resistance by regulating miR-373-3p/CPEB4 axis in glioma through PI3K/Akt pathway [J ] . Mol Cell Biochem ， 2021 ， 476 （ 2 ）： 699 - 713 ．

Zhou QY ， Xie Y ， Wang L ， et al . LncRNA EWSAT1 upregulates CPEB4 via miR-330-5p to promote cervical cancer development [J ] . Mol Cell Biochem ， 2020 ， 471 （ 1 ）： 177 - 188 ．

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