hsa_circ_0011946靶向miR-767-3p调控宫颈癌细胞增殖、迁移和侵袭

李文亚; 谢程; 彭莉

doi:10.11659/jjssx.02E023047

您当前的位置：

首页 >

文章列表页 >

hsa_circ_0011946靶向miR-767-3p调控宫颈癌细胞增殖、迁移和侵袭

基础研究 | 更新时间：2024-02-02

- hsa_circ_0011946靶向miR-767-3p调控宫颈癌细胞增殖、迁移和侵袭
- hsa_circ_0011946 regulates the proliferation, migration and invasion of cervical cancer cells via targeting miR-767-3p
- 局解手术学杂志 2024年33卷第2期页码：118-124
- 作者机构：
  
  1.长江大学附属仙桃市第一人民医院妇产科，湖北仙桃 433000
  2.长江大学附属仙桃市第一人民医院肾内科，湖北仙桃 433000
- 作者简介：
  
  谢程，E-mail：34803025@qq.com
- 基金信息：
  
  湖北省卫生健康委员会基金(WJ2021AB046)
- DOI：10.11659/jjssx.02E023047
  中图分类号： R737.33
- 纸质出版日期：2024-02-25，
  
  收稿日期：2023-02-10，
扫描看全文
李文亚,谢程,彭莉.hsa_circ_0011946靶向miR-767-3p调控宫颈癌细胞增殖、迁移和侵袭[J].局解手术学杂志,2024,33(02):118-124.

LI Wen-ya,XIE Cheng,PENG Li.hsa_circ_0011946 regulates the proliferation, migration and invasion of cervical cancer cells via targeting miR-767-3p[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(02):118-124.
李文亚,谢程,彭莉.hsa_circ_0011946靶向miR-767-3p调控宫颈癌细胞增殖、迁移和侵袭[J].局解手术学杂志,2024,33(02):118-124. DOI： 10.11659/jjssx.02E023047.

LI Wen-ya,XIE Cheng,PENG Li.hsa_circ_0011946 regulates the proliferation, migration and invasion of cervical cancer cells via targeting miR-767-3p[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(02):118-124. DOI： 10.11659/jjssx.02E023047.

摘要

目的

探讨hsa_circ_0011946靶向miR-767-3p在宫颈癌进展中的作用。

方法

RT-qPCR分析hsa_circ_0011946、miR-767-3p在宫颈癌组织、癌旁正常组织、人宫颈上皮永生化细胞（H8）及宫颈癌细胞（SiHa、HeLa、Caski）中的表达水平。分别用si-NC、si-hsa_circ_0011946、miR-NC、miR-767-3p、pcDNA、pcDNA-hsa_circ_0011946、anti-miR-NC+si-hsa_circ_0011946、anti-miR-767-3p+si-hsa_circ_0011946转染SiHa细胞，并设为si-NC组、si-hsa_circ_0011946组、miR-NC组、miR-767-3p组、pcDNA组、pcDNA-hsa_circ_0011946组、anti-miR-NC+si-hsa_circ_0011946组、anti-miR-767-3p+si-hsa_circ_0011946组，未转染的细胞作为NC组。采用RT-qPCR检测各组SiHa细胞中hsa_circ_0011946和miR-767-3p的表达；CCK-8法检测细胞活力；平板克隆形成实验检测细胞克隆数；Transwell实验检测细胞迁移和侵袭数；Western blot检测MMP-2、MMP-9蛋白表达。circular RNA interactome预测miR-767-3p与hsa_circ_0011946的结合位点，双荧光素酶报告基因实验分析hsa_circ_0011946和miR-767-3p的靶向关系。

结果

与癌旁正常组织比较，宫颈癌组织中hsa_circ_0011946表达水平显著升高（

0.05），miR-767-3p表达水平显著降低（

0.05）。与H8细胞比较，SiHa、HeLa、Caski细胞中hsa_circ_0011946表达水平显著升高（

0.05），miR-767-3p表达水平显著降低（

0.05）。与NC组比较，si-hsa_circ_0011946组SiHa细胞hsa_circ_0011946表达水平、吸光度（A）值、克隆数、迁移数、侵袭数及MMP-2、MMP-9蛋白表达水平显著降低/减少（

0.05）。与miR-NC组比较，miR-767-3p组SiHa细胞miR-767-3p表达水平显著升高（

0.05），A值、克隆数、迁移数、侵袭数及MMP-2、MMP-2蛋白表达水平显著降低/减少（

0.05）。与pcDNA组比较，pcDNA-hsa_circ_0011946组SiHa细胞miR-767-3p表达水平显著降低（

0.05），hsa_circ_0011946表达水平显著升高（

0.05）。共转染miR-767-3p mimics和WT-hsa_circ_0011946的SiHa细胞相对荧光素酶活性低于共转染miR-NC和WT-hsa_circ_0011946（

0.05）。hsa_circ_0011946与miR-767-3p直接特异性结合。与anti-miR-NC+si-hsa_circ_0011946组比较，anti-miR-767-3p+si-hsa_circ_0011946组SiHa细胞miR-767-3p表达水平显著降低（

0.05），A值、克隆数、迁移数、侵袭数及MMP-2、MMP-9蛋白表达水平显著升高/增加（

0.05）。

结论

干扰hsa_circ_0011946通过靶向上调miR-767-3p抑制宫颈癌细胞的增殖、迁移和侵袭。

Abstract

Objective

To investigate the role of hsa_circ_0011946 targeting miR-767-3p in the progression of cervical cancer.

Methods

The expression levels of hsa_circ_0011946 and miR-767-3p in cervical cancer tissues， adjacent tissues， immortalized human cervical epithelial cells （H8） and cervical cancer cells （SiHa， HeLa， and Cashi） were determined by RT-qPCR. SiHa cells were transfected with si-NC， si-hsa_circ_0011946， miR-NC， miR-767-3p， pcDNA， pcDNA-hsa_circ_0011946， anti-miR-NC+si-hsa_circ_0011946， anti-miR-767-3p+si-hsa_circ_0011946， respectively， as the si-NC group， the si-hsa_circ_0011946 group， the miR-NC group， the miR-767-3p group， the pcDNA group， the pcDNA-hsa_circ_0011946 group， the anti-miR-NC+si-hsa_circ_0011946 group， and the anti-miR-767-3p+si-hsa_circ_0011946 group， and the untransfected cells were used as the NC group. The expression of hsa_circ_0011946 and miR-767-3p of SiHa cells in each group was detected by RT-qPCR， the cell viability was detected by CCK-8， the number of cell clone was detected by plate clone formation assay， the cell migration and invasion numbers were detected by Transwell assay， and the protein expression of MMP-2 and MMP-9 was detected by Western blot. The binding site of miR-767-3p to hsa_circ_0011946 was predicted by circular RNA interactome， and the targeted relationship between hsa_circ_0011946 and miR-767-3p was analyzed by dual luciferase reporter assay.

Results

Compared with the adjacent tissues， the expression level of hsa_circ_0011946 in the cervical cancer tissues was significantly increased （

0.05）， while the expression level of miR-767-3p was significantly decreased （

0.05）. Compared with H8 cells， the expression levels of hsa_circ_0011946 in SiHa， HeLa and Caski cells were significantly increased （

0.05）， while the expression levels of miR-767-3p were significantly decreased （

0.05）. Compared with the NC group， the expression level of hsa_circ_0011946，absorbance （A） value， number of clone， number of migration， number of invasion and the protein expression levels of MMP-2 and MMP-9 were significantly decreased in SiHa cells in the miR-767-3p group （

0.05）. Compared with the miR-NC group， the expression level of miR-767-3p in SiHa cells in the miR-767-3p group was significantly increased （

0.05）， and the cell A value， number of clone， number of migration， number of invasion and the protein expression levels of MMP-2 and MMP-9 were significantly decreased （

0.05）. Compared with the pcDNA group， the expression level of miR-767-3p in SiHa cells in the pcDNA-hsa_circ_0011946 group was significantly decreased （

0.05）， and the expression level of hsa_circ_0011946 was significantly increased （

0.05）. The relative luciferase activity of SiHa cells co-transfected with miR-767-3p mimics and WT-hsa_circ_0011946 was lower than that of co-transfected with miR-NC and WT-hsa_circ_0011946 （

0.05）. hsa_circ_0011946 bound to miR-767-3p directly and specifically. Compared with the anti-miR-NC+si-hsa_circ_0011946 group， the expression level of miR-767-3p in SiHa cells in the anti-miR-767-3p+si-hsa_circ_0011946 group was significantly decreased （

0.05）， and the cell A value， number of clone， number of migration， number of invasion and protein expression levels of MMP-2 and MMP-9 were significantly increased （

0.05）.

Conclusion

Interfering hsa_circ_0011946 can inhibit the proliferation， migration and invasion of cervical cancer cells through targeted up-regulation of miR-767-3p.

关键词

hsa_circ_0011946miR-767-3p宫颈癌增殖迁移侵袭

Keywords

hsa_circ_0011946miR-767-3pcervical cancerproliferationmigrationinvasion

references

Bhatla N，Aoki D，Sharma DN，et al.Cancer of the cervix uteri：2021 update［J］.Int J Gynaecol Obstet，2021，155Suppl 1（Suppl 1）：28-44.doi：10.1002/ijgo.13865http://dx.doi.org/10.1002/ijgo.13865.

Ma B，Wang S，Wu W，et al.Mechanisms of circRNA/lncRNA-miRNA interactions and applications in disease and drug research［J］.Biomed Pharmacother，2023，162（2）：114672.doi：10.1016/j.biopha.2023.114672http://dx.doi.org/10.1016/j.biopha.2023.114672.

Guo X，Chen S，Wang S，et al.CircRNA-based cervical cancer prognosis model，immunological validation and drug prediction［J］.Curr Oncol，2022，29（11）：7994-8018.doi：10.3390/curroncol29110633http://dx.doi.org/10.3390/curroncol29110633.

Wang S，Zhang S.Systematic analyses of a novel circRNA-related miRNAs prognostic signature for cervical cancer［J］.Genet Mol Biol，2022，45（2）：e20210405.doi：10.1590/1678-4685-GMB-2021-0405http://dx.doi.org/10.1590/1678-4685-GMB-2021-0405.

Zhou J，Zhang WW，Peng F，et al.Downregulation of hsa_circ_0011946 suppresses the migration and invasion of the breast cancer cell line MCF-7 by targeting RFC3［J］.Cancer Manag Res，2018，10（2）：535-544.doi：10.2147/CMAR.S155923http://dx.doi.org/10.2147/CMAR.S155923.

Dudea-Simon M，Mihu D，Pop LA，et al.Alteration of gene and miRNA expression in cervical intraepithelial neoplasia and cervical cancer［J］.Int J Mol Sci，2022，23（11）：15-32.doi：10.3390/ijms23116054http://dx.doi.org/10.3390/ijms23116054.

Deng ZM，Chen GH，Dai FF，et al.The clinical value of miRNA-21 in cervical cancer：a comprehensive investigation based on microarray datasets［J］.PLoS One，2022，17（4）：e0267108.doi：10.1371/journal.pone.0267108http://dx.doi.org/10.1371/journal.pone.0267108.

Kreth S，Limbeck E，Hinske LC，et al.In human glioblastomas transcript elongation by alternative polyadenylation and miRNA targeting is a potent mechanism of MGMT silencing［J］.Acta Neuropathol，2013，125（5）：671-681.doi：10.1007/s00401-013-1081-1http://dx.doi.org/10.1007/s00401-013-1081-1.

Wan YL，Dai HJ，Liu W，et al.miR-767-3p inhibits growth and migration of lung adenocarcinoma cells by regulating CLDN18［J］.Oncol Res，2018，26（4）：637-644.doi：10.3727/096504017X15112639918174http://dx.doi.org/10.3727/096504017X15112639918174.

Meng QH，Li Y，Kong C，et al.Circ_0000388 exerts oncogenic function in cervical cancer cells by regulating miR-337-3p/TCF12 axis［J］.Cancer Biother Radiopharm，2021，36（1）：58-69.doi：10.1089/cbr.2019.3159http://dx.doi.org/10.1089/cbr.2019.3159.

Liu J，Wang D，Long Z，et al.CircRNA8924 promotes cervical cancer cell proliferation，migration and invasion by competitively binding to miR-518d-5p/519-5p family and modulating the expression of CBX8［J］.Cell Physiol Biochem，2018，48（1）：173-184.doi：10.1159/000491716http://dx.doi.org/10.1159/000491716.

Xu J，Zhang Y，Huang Y，et al.circEYA1 functions as a sponge of miR-582-3p to suppress cervical adenocarcinoma tumorigenesis via upregulating CXCL14［J］.Mol Ther Nucleic Acids，2020，22：1176-1190.doi：10.1016/j.omtn.2020.10.026http://dx.doi.org/10.1016/j.omtn.2020.10.026.

Chen M，Ai G，Zhou J，et al.circMTO1 promotes tumorigenesis and chemoresistance of cervical cancer via regulating miR-6893［J］.Biomed Pharmacother，2019，117：109064.doi：10.1016/j.biopha.2019.109064http://dx.doi.org/10.1016/j.biopha.2019.109064.

Ren L，Zhai H，Wang XL，et al.Hsa_circ_0011946 promotes the migration and invasion of hepatocellular carcinoma by inducing EMT process［J］.Eur Rev Med Pharmacol Sci，2020，24（3）：1108-1115.doi：10.26355/eurrev_202002_20161http://dx.doi.org/10.26355/eurrev_202002_20161.

Zhou P，Song NC，Zheng ZK，et al.MMP2 and MMP9 contribute to lung ischemia-reperfusion injury via promoting pyroptosis in mice［J］.BMC Pulm Med，2022，22（1）：230.doi：10.1186/s12890-022-02018-7http://dx.doi.org/10.1186/s12890-022-02018-7.

Akol I，Kalogeraki E，Pielecka-Fortuna J，et al.MMP2 and MMP9 activity is crucial for adult visual cortex plasticity in healthy and stroke-affected mice［J］.J Neurosci，2022，42（1）：16-32.doi：10.1523/JNEUROSCI.0902-21.2021http://dx.doi.org/10.1523/JNEUROSCI.0902-21.2021.

Wang Y，Miao C，Gao X.TCEB3 is regulated by circ-0000212/miR-140-3p axis to promote the progression of cervical cancer［J］.Onco Targets Ther，2021，14：2853-2865.doi：10.2147/OTT.S278710http://dx.doi.org/10.2147/OTT.S278710.

Tang Q，Chen Z，Zhao L，et al.Circular RNA hsa_circ_0000515 acts as a miR-326 sponge to promote cervical cancer progression through up-regulation of ELK1［J］.Aging （Albany NY），2019，11（22）：9982-9999.doi：10.18632/aging.102356http://dx.doi.org/10.18632/aging.102356.

Xu X，Zhou X，Gao C，et al.Hsa_circ_0018818 knockdown suppresses tumorigenesis in non-small cell lung cancer by sponging miR-767-3p［J］.Aging （Albany NY），2020，12（9）：7774-7785.doi：10.18632/aging.103089http://dx.doi.org/10.18632/aging.103089.

Jiang W，Wen D，Gong L，et al.Circular RNA hsa_circ_0000673 promotes hepatocellular carcinoma malignance by decreasing miR-767-3p targeting SET［J］.Biochem Biophys Res Commun，2018，500（2）：211-216.doi：10.1016/j.bbrc.2018.04.041http://dx.doi.org/10.1016/j.bbrc.2018.04.041.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

CDCA3在上皮性卵巢癌中的表达及意义

沉默PROX1基因对甲状腺乳头状癌TPC-1细胞的影响

miR-129靶向调节Twist1抑制乳腺癌细胞的增殖、迁移和侵袭

lncRNA MIR4435-2HG靶向miR-376a-3p调控胆管癌细胞生物学行为的机制研究

阿魏酸通过调节PTEN/PI3K/AKT信号通路抑制急性T淋巴细胞白血病进展