RNA传感器IFIH1对HPV阳性的宫颈癌细胞增殖、迁移和侵袭的影响

喻琳; 罗莹; 吴迪; 洪世垣

doi:10.16016/j.2097-0927.202203089

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RNA传感器IFIH1对HPV阳性的宫颈癌细胞增殖、迁移和侵袭的影响

基础医学 | 更新时间：2026-01-09

- RNA传感器IFIH1对HPV阳性的宫颈癌细胞增殖、迁移和侵袭的影响
- Effect of RNA sensor IFIH1 on proliferation, migration and invasion of HPV positive cervical cancer cells
- 陆军军医大学学报 2022年44卷第16期页码：1651-1660
- 作者机构：
  
  400016 重庆，重庆医科大学生命科学研究院
- 作者简介：
  
  [洪世垣，E-mail：hongshiyuan@cqmu.edu.cnHONG Shiyuan, E-mail: hongshiyuan@cqmu.edu.cn
- 基金信息：
- DOI：10.16016/j.2097-0927.202203089
  中图分类号： R341;R730.23;R737.33
- 收稿：2022-03-10，
  
  修回：2022-05-03，
  
  纸质出版：2022-08-30
- 稿件说明：
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喻琳, 罗莹, 吴迪, 等. RNA传感器IFIH1对HPV阳性的宫颈癌细胞增殖、迁移和侵袭的影响[J]. 陆军军医大学学报, 2022,44(16):1651-1660.

Lin YU, Ying LUO, Di WU, et al. Effect of RNA sensor IFIH1 on proliferation, migration and invasion of HPV positive cervical cancer cells[J]. Journal of Army Medical University, 2022, 44(16): 1651-1660.
喻琳, 罗莹, 吴迪, 等. RNA传感器IFIH1对HPV阳性的宫颈癌细胞增殖、迁移和侵袭的影响[J]. 陆军军医大学学报, 2022,44(16):1651-1660. DOI： 10.16016/j.2097-0927.202203089.

Lin YU, Ying LUO, Di WU, et al. Effect of RNA sensor IFIH1 on proliferation, migration and invasion of HPV positive cervical cancer cells[J]. Journal of Army Medical University, 2022, 44(16): 1651-1660. DOI： 10.16016/j.2097-0927.202203089.

摘要

目的

探讨RNA传感器干扰素诱导的解旋酶C结构域蛋白1(interferon-induced helicase C domain protein 1，IFIH1)对人乳头瘤病毒18型(human papillomavirus 18，HPV18)阳性的人宫颈癌细胞HeLa增殖、迁移和侵袭的影响。

方法

利用GEPIA数据库分析IFIH1在正常宫颈组织和宫颈癌组织中的表达。Western blot检测IFIH1在C33A和HeLa细胞中的表达。将HPV18基因组转染到正常上皮细胞HaCaT中，并利用Western blot和实时定量PCR检测IFIH1的表达水平。利用实时无标记动态细胞分析技术和CCK8法检测细胞的增殖能力。划痕愈合实验、Transwell迁移实验和侵袭实验分别检测细胞的迁移能力和侵袭能力。Western blot和免疫荧光实验检测STAT3和磷酸化STAT3的蛋白表达和定位。

结果

GEPIA数据库分析显示IFIH1在宫颈癌组织中的表达量明显高于正常宫颈组织(

0.05)；相比于C33A细胞，HeLa细胞中IFIH1的表达水平明显增加(

0.01)；与正常HaCaT细胞相比，转染HPV18的HaCaT细胞中IFIH1的表达增加(

0.01)；与阴性对照相比，敲低IFIH1明显抑制HeLa细胞的增殖、迁移和侵袭能力，而过表达IFIH1则促进C33A细胞的增殖、迁移和侵袭(

0.01)；敲低IFIH1后，磷酸化STAT3蛋白的表达减少(

0.01)。

结论

IFIHI在被HPV感染的宫颈癌细胞中表达增加，这将促进细胞的增殖、迁移和侵袭能力，可能与激活STAT3有关。

Abstract

Objective

To investigate the effect of RNA sensor interferon-induced helicase C domain protein 1 (IFIH1) on the proliferation

migration and invasion of HPV18 positive human cervical cancer HeLa cell line.

Methods

The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to analyze the expression of IFIH1 in normal cervical tissues and cervical cancer tissues. The expression of IFIH1 in C33A cells and HeLa cells was detected by Western blotting. After the HPV18 genome was transfected into normal epithelial HaCaT cells

the expression of IFIH1 was detected by Western blotting and real-time quantitative PCR. The ability of cell proliferation was detected by real time cell analysis (RTCA) system and CCK8 assay

and the ability of cell migration and invasion were examined by wound scratch healing assay and transwell assay. The expression and localization of STAT3 and phosphorylated STAT3 were analyzed by Western blotting and immunofluorescence assay.

Results

GEPIA database analysis showed that the expression of IFIH1 was significantly higher in cervical cancer tissues than normal cervical tissues (

0.05). Compared with the C33A cells

the expression of IFIH1 in HeLa cells was significantly increased (

0.01). And its expression was increased in the HaCaT cells with HPV18 genome transfection than the normal HaCaT cells (

0.01). IFIH1 knockdown resulted in obviously decreased proliferation

migration and invasion abilities in HeLa cells when compared with the negative control cells

while overexpression of IFIH1 promoted the proliferation

migration and invasion in the C33A cells (

0.01). Meanwhile

the expression of phosphorylated STAT3 protein was decreased in HeLa cells with IFIH1 knockdown (

0.01).

Conclusion

The expression of IFIH1 is increased in cervical cancer cells infected by HPV

which promotes cell proliferation

migration and invasion and may be related to the activation of STAT3.

关键词

Keywords

references

BRAY F, FERLAY J, SOERJOMATARAM I, et al . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185countries[J ] . CA Cancer J Clin, 2018, 68(6): 394-424. DOI:10.3322/caac.21492.

WALBOOMERS J M, JACOBS M V, MANOS M M, et al . Human papillomavirus is a necessary cause of invasive cervical cancer worldwide[J ] . J Pathol, 1999, 189(1): 12-19. DOI:10.1002/(SICI)1096-9896(199909)189: 112: AID-PATH431 > 3.0.CO;2-F.

BODILY J, LAIMINS L A. Persistence of human papillomavirus infection: keys to malignant progression[J]. Trends Microbiol, 2011, 19(1): 33-39. DOI:10.1016/j.tim.2010.10.002.

HEMMAT N, BANNAZADEH BAGHI H. Association of human papillomavirus infection and inflammation in cervical cancer[J]. Pathog Dis, 2019, 77(5): ftz048. DOI:10.1093/femspd/ftz048.

SENBA M, MORI N. Mechanisms of virus immune evasion lead to development from chronic inflammation to cancer formation associated with human papillomavirus infection[J]. Oncol Rev, 2012, 6(2): e17. DOI:10.4081/oncol.2012.e17.

FENSTERL V, CHATTOPADHYAY S, SEN G C. No love lost between viruses and interferons[J]. Annu Rev Virol, 2015, 2(1): 549-572.

DIAS JUNIOR A G, SAMPAIO N G, REHWINKEL J. A balancing act: MDA5 in antiviral immunity and autoinflammation[J]. Trends Microbiol, 2019, 27(1): 75-85. DOI:10.1016/j.tim.2018.08.007.

WU Y B, WU X Q, WU L H, et al . The anticancer functions of RIG -I-like receptors, RIG-I and MDA5, and their applications in cancer therapy[J ] . Transl Res, 2017, 190: 51-60. DOI:10.1016/j.trsl.2017.08.004.

CHAN Y K, GACK M U. Viral evasion of intracellular DNA and RNA sensing[J]. Nat Rev Microbiol, 2016, 14(6): 360-373. DOI: 10.1038/nrmicro.2016.45.

PHAM A M, SANTA MARIA F G, LAHIRI T, et al . PKR transduces MDA5-dependent signals for type I IFN induction[J ] . PLoS Pathog, 2016, 12(3): e1005489. DOI:10.1371/journal.ppat.1005489.

LU H L, LIAO F. Melanoma differentiation-associated gene 5 senses hepatitis B virus and activates innate immune signaling to suppress virus replication[J]. J Immunol, 2013, 191(6): 3264-3276. DOI:10.4049/jimmunol.1300512.

MELCHJORSEN J, RINTAHAKA J, SØBY S, et al . Early innate recognition of Herpes simplex virus in human primary macrophages is mediated via the MDA5/MAVS-dependent and MDA5/MAVS/RNA polymerase Ⅲ-independent pathways[J ] . J Virol, 2010, 84(21): 11350-11358. DOI:10.1128/JVI.01106-10.

PICHLMAIR A, SCHULZ O, TAN C P, et al . Activation of MDA5 requires higher-order RNA structures generated during virus infection[J ] . J Virol, 2009, 83(20): 10761-10769. DOI:10.1128/JVI.00770-09.

ROULOIS D, LOO YAU H, SINGHANIA R, et al . DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts[J ] . Cell, 2015, 162(5): 961-973. DOI:10.1016/j.cell.2015.07.056.

PALCHETTI S, STARACE D, DE CESARIS P, et al . Transfected poly(I: C) activates different dsRNA receptors, leading to apoptosis or immunoadjuvant response in androgen-independent prostate cancer cells[J ] . J Biol Chem, 2015, 290(9): 5470-5483. DOI:10.1074/jbc.M114.601625.

INAO T, HARASHIMA N, MONMA H, et al . Antitumor effects of cytoplasmic delivery of an innate adjuvant receptor ligand, poly(I: C), on human breast cancer[J ] . Breast Cancer Res Treat, 2012, 134(1): 89-100. DOI:10.1007/s10549-011-1930-3.

PIERSMA S J. Immunosuppressive tumor microenvironment in cervical cancer patients[J]. Cancer Microenviron, 2011, 4(3): 361-375. DOI:10.1007/s12307-011-0066-7.

LIN L, SU Z, LEBEDEVA I V, et al . Activation of Ras/Raf protects cells from melanoma differentiation-as sociated gene-5-induced apoptosis[J ] . Cell Death Differ, 2006, 13(11): 1982-1993. DOI:10.1038/sj.cdd.4401899.

KANG D C, GOPALKRISHNAN R V, LIN L, et al . Expression analysis and genomic characterization of human melanoma differentiation associated gene-5, mda-5: a novel type Ⅰ interferon-responsive apoptosis-inducing gene[J ] . Oncogene, 2004, 23(9): 1789-1800. DOI:10.1038/sj.onc.1207300.

HSU W M, HUANG C C, LEE H Y, et al . MDA5 complements TLR3 in suppression of neuroblastoma[J ] . Oncotarget, 2015, 6(28): 24935-24946. DOI:10.18632/oncotarget.4511.

DUEWELL P, BELLER E, KIRCHLEITNER S V, et al . Targeted activation of melanoma differentiation-associated protein 5 (MDA5) for immunotherapy of pancreatic carcinoma[J ] . Oncoimmunology, 2015, 4(10): e1029698. DOI: 10.1080/2162402X.2015.1029698.

PENG S, GENG J L, SUN R, et al . Polyinosinic-polycytidylic acid liposome induces human hepatoma cells apoptosis which correlates to the up-regulation of RIG-I like receptors[J ] . Cancer Sci, 2009, 100(3): 529-536. DOI:10.1111/j.1349-7006.2008.01062.x.

BESCH R, POECK H, H OHENAUER T, et al . Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon-independent apoptosis in human melanoma cells[J ] . J Clin Invest, 2009, 119(8): 2399-2411. DOI:10.1172/JCI37155.

CHAI E Z, SHANMUGAM M K, ARFUSO F, et al . Targeting transcription factor STAT3 for cancer prevention and therapy[J ] . Pharmacol Ther, 2016, 162: 86-97. DOI:10.1016/j.pharmthera.2015.10.004.

TURKSON J. STAT proteins as novel targets for cancer drug discovery[J]. Expert Opin Ther Targets, 2004, 8(5): 409-422. DOI:10.1517/14728222.8.5.409.

DIEN J, AMIN H M, CHIU N, et al . Signal transducers and activators of transcription-3 up-regulates tissue inhibitor of metalloproteinase-1 expression and decreases invasiveness of breast cancer[J ] . Am J Pathol, 2006, 169(2): 633-642. DOI:10.2353/ajpath.2006.051109.

KUSABA T, NAKAYAMA T, YAMAZUMI K, et al . Expression of p-STAT3 in human colorectal adenocarcinoma and adenoma; correlation with clinicopathological factors[J ] . J Clin Pathol, 2005, 58(8): 833-838. DOI:10.1136/jcp.2004.023416.

XU Y H, LU S. A meta-analysis of STAT3 and phospho-STAT3 expression and survival of patients with non-small-cell lung cancer[J]. Eur J Surg Oncol, 2014, 40(3): 311-317. DOI:10.1016/j.ejso.2013.11.012.

SHI S, MA H Y, ZHANG Z G. Clinicopathological and prognostic value of STAT3/p-STAT3 in cervical cancer: a meta and bioinformatics analysis[J]. Pathol Res Pract, 2021, 227: 153624. DOI:10.1016/j.prp.2021.153624.

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