The Journal of Practical Medicine >

2024 , Vol. 40 >Issue 2: 146 - 152

DOI: https://doi.org/10.3969/j.issn.1006-5725.2024.02.004

Feature Reports：carcinoma of cervix

HPV16 E6 regulates miR-23a expression and promotes invasion and migration of cervical cancer cells

  • Min WANG ,
  • Dan MU ,
  • Dejun KONG ,
  • Li YANG ,
  • Lu YE ,
  • Dan HE
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  • Department of Oncology，the Second Affiliated Hospital of Chengdu Medical College/No. 416 Hospital of Nuclear Industry，Chengdu 610000，China

Received date: 2023-07-26

  Online published: 2024-03-06

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Abstract

Objective To investigate the effects of high-risk human papillomavirus 16 E6 protein （HPV16 E6 protein） on invasion and migration of cervical cancer SiHa cells via regulating the expression of expression miR-23a. Methods Tissue samples from 100 patients with cervical cancer HPV-negative， 100 HPV-positive patients， and 100 paracancerous normal tissues were collected； cervical cancer SiHa cells were divided into blank group， E6 overexpression group， negative transfection group， and E6 + miR-23a mimics group. The expression of miR-23a and HPV16 E6 mRNA were detected by qRT-PCR； MTT assay was used to detect the cell proliferation inhibition rate； flow cytometry to detect the apoptosis； Transwell chamber assay to detect cell invasion， and scratch test to detect the ability of cell migration. The expression of HPV16 E6， apoptosis related proteins （Caspase-3， Bax， Bcl-2）， and migration related proteins （MMP-2， MMP-9） was detected by WB. Results The expression level of miR-23a was decreased in cervical cancer tissues， and that was lower in HPV positive cervical cancer tissues. Overexpression of E6 decreased the expression level of miR-23a， cell proliferation inhibition rate， apoptosis rate， Caspase-3 and Bax protein expression， and increased the expression of Bcl-2 protein， scratch healing rate， invasion cell number， MMP-2， MMP-9 protein expression （P < 0.05）； miR-23a mimics reversed the effects of E6 overexpression on the above indicators. Conclusion HPV16 E6 promotes the invasion and migration of cervical cancer cells， which may be related to the regulation of miR-23a expression.

Key words： human papillomavirus 16 E6 protein; miR-23a; cervical cancer; invasion; migration

Cite this article

Min WANG , Dan MU , Dejun KONG , Li YANG , Lu YE , Dan HE . HPV16 E6 regulates miR-23a expression and promotes invasion and migration of cervical cancer cells[J]. The Journal of Practical Medicine, 2024 , 40(2) : 146 -152 . DOI: 10.3969/j.issn.1006-5725.2024.02.004

References

1 KATE T S， JULIA S， MICHAEL C， et al. Impact of scaled up human papillomavirus vaccination and cervical screening and the potential for global elimination of cervical cancer in 181 countries， 2020-99： a modelling study［J］. Lancet Oncol， 2019， 20（3）：394-407. doi:10.1016/s1470-2045(18)30836-2
2 YANG Y， CHE Y， ZHAO Y， et al. Prevention and treatment of cervical cancer by a single administration of human papillomavirus peptide vaccine with CpG oligodeoxynucleotides as an adjuvant in vivo［J］. Int Immunopharmacol， 2019， 69（1）：279-288. doi:10.1016/j.intimp.2019.01.024
3 WANG H， PARK S， LEE D， et al. Prevalence of type-specific oncogenic human papillomavirus infection assessed by HPV E6/E7 mRNA among women with high-grade cervical lesions［J］. Int J Infect Dis， 2015， 37（1）：135-142. doi:10.1016/j.ijid.2015.06.018
4 LAI S Y， GUAN H M， LIU J， et al. Long noncoding RNA SNHG12 modulated by human papillomavirus 16 E6/E7 promotes cervical cancer progression via ERK/Slug pathway［J］. J Cell Physiol， 2020， 235（11）：7911-7922. doi:10.1002/jcp.29446
5 LIU J， ZHAO H， ZHANG Q， et al. Human papillomavirus type 16 E7 oncoprotein-induced upregulation of lysine-specific demethylase 5A promotes cervical cancer progression by regulating the microRNA-424-5p/suppressor of zeste 12 pathway［J］. Exp Cell Res， 2020， 396（1）：112277. doi:10.1016/j.yexcr.2020.112277
6 WANG J， LIU S， PAN T， et al. Long non-coding RNA ZNF674-AS1 regulates miR-23a/E-cadherin axis to suppress the migration and invasion of non-small cell lung cancer cells［J］. Transl Cancer Res， 2021， 10（9）：4116-4124. doi:10.21037/tcr-21-1499
7 ZHOU L， JIANG H， LIN L， et al. lncRNA GAS5 suppression of the malignant phenotype of ovarian cancer via the miR-23a-WT1 axis［J］. Ann Transl Med， 2023， 11（2）：119. doi:10.21037/atm-22-6394
8 林楠，许子琪，蔡雁，等. miR-23a在宫颈癌患者组织血清中的表达及相关性分析［J］. 现代生物医学进展， 2021， 21（8）：1507-1510.
9 赵文君，左娜，葛彩云，等. HPV16E6对ZEB1介导的宫颈癌细胞上皮间质转化的促进作用［J］. 武汉大学学报（医学版），2018，39（5）：693-698.
10 ABDULLAH H， ISMAIL I， SUPPIAN R， et al. Natural gallic acid and methyl gallate induces apoptosis in hela cells through regulation of intrinsic and extrinsic protein expression［J］. Int J Mol Sci， 2023， 24（10）：8495. doi:10.3390/ijms24108495
11 LUO A， LAN X， QIU Q， et al. LncRNA SFTA1P promotes cervical cancer progression by interaction with PTBP1 to facilitate TPM4 mRNA degradation［J］. Cell Death Dis， 2022， 13（11）：936. doi:10.1038/s41419-022-05359-7
12 PANG Y S， ZHANG Z H， WANG Z， et al. Platelet endothelial aggregation receptor-1 regulates bovine muscle satellite cell migration and differentiation via integrin beta-1 and focal adhesion kinase［J］. Cell Adhes Migr， 2019， 13（1）：192-202. doi:10.1080/19336918.2019.1619434
13 NABIRYE J， OKWI L A， NUWEMATSIKO R， et al. Health system factors influencing uptake of Human Papilloma Virus （HPV vaccine among adolescent girls 9-15 years in Mbale District， Uganda［J］. BMC Public Health， 2020， 20（1）：171. doi:10.1186/s12889-020-8302-z
14 FREDDIE B， JACQUES F， ISABELLE S， et al. Global cancer statistics 2018： GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］. CA Cancer J Clin， 2018， 68（6）：394-424. doi:10.3322/caac.21492
15 杨利利，胡强夫，闵娜，等. 右美托咪定对宫颈癌细胞HSP90/ERK通路及顺铂敏感性的影响［J］. 实用医学杂志，2022，38（16）：2019-2023. doi:10.3969/j.issn.1006-5725.2022.16.007
16 苗小艳，孔繁斗，孙悦，等. HPV16 E6对HeLa细胞中Rap1GAP蛋白水平下调的研究［J］. 中国微生态学杂志，2015，27（5）：527-530+538.
17 王旭，徐静，王笑笑，等. miR-218-5p靶向VEGFA基因促进宫颈癌HeLa细胞凋亡并抑制迁移［J］. 实用医学杂志，2022，38（15）：1878-1883. doi:10.3969/j.issn.1006-5725.2022.15.006
18 支亚丽，张诗蒙，栗俊杰，等. 宫颈脱落细胞中miR-23b、miR-34a在宫颈癌诊断中的作用［J］. 中国妇幼保健，2018，33（14）：3304-3306.
19 种楠，李勤，冯艳红，等. 槲皮素抑制宫颈癌Siha细胞增殖和侵袭实验研究［J］. 中华实用诊断与治疗杂志，2019，33（2）：113-116.
20 MA S， LIU M， XU Z， et al. A double feedback loop mediated by microRNA-23a/27a/24-2 regulates M1 versus M2 macrophage polarization and thus regulates cancer progression［J］. Oncotarget， 2016， 7（12）：13502-13519. doi:10.18632/oncotarget.6284
21 王军，袁纯辉，孙红，等. 高危型人乳头瘤病毒16 E6蛋白通过外泌体传递热休克蛋白70调控巨噬细胞介导宫颈癌细胞增殖、侵袭和迁移［J］. 中华微生物学和免疫学杂志，2020，40（7）：538-546. doi:10.3760/cma.j.cn112309-20190822-00267
22 ANJA H， DANIELA S， SANDRA B， et al. Dependence of intracellular and exosomal microRNAs on viral E6/E7 oncogene expression in HPV-positive tumor cells［J］. PLoS Pathog， 2015， 11（3）：e1004712. doi:10.1371/journal.ppat.1004712
23 YEUNG C L， TSANG T Y， YAU P L， et al. Human papillomavirus type 16 E6 suppresses microRNA-23b expression in human cervical cancer cells through DNA methylation of the host gene C9orf3［J］. Oncotarget， 2017， 8（7）：12158-12173. doi:10.18632/oncotarget.14555
24 邓淑文，夏红星. GTPBP4基因沉默介导EGFR/PI3K/AKT信号通路对顺铂诱导的胃癌细胞凋亡的调控机制［J］. 中国免疫学杂志，2020，36（16）：1-14. doi:10.3969/j.issn.1000-484X.2020.22.012
25 ZHANG J， WANG R， CHENG L， et al. Celastrol inhibit the proliferation， invasion and migration of human cervical HeLa cancer cells through down-regulation of MMP-2 and MMP-9［J］. J Cell Mol Med， 2021， 25（11）：5335-5338. doi:10.1111/jcmm.16488
26 WANG C， WANG Y， LIU C， et al. Kinetochore-associated protein 1 promotes the invasion and tumorigenicity of cervical cancer cells via matrix metalloproteinase-2 and matrix metalloproteinase-9［J］. Bioengineered， 2022， 13（4）：9495-9507. doi:10.1080/21655979.2022.2061144
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