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微小RNA-21通过靶向组织金属蛋白酶抑制因子3促进宫颈癌的增殖、迁移和侵袭。

MicroRNA-21 promotes proliferation, migration, and invasion of cervical cancer through targeting TIMP3.

作者信息

Zhang Zhan, Wang Jinming, Wang Xiaofang, Song Wanyu, Shi Ying, Zhang Linlin

机构信息

The Third Affiliated Hospital of Zhengzhou University, 7 Front Kang-fu Road, Zhengzhou, 450000, Henan, People's Republic of China.

Shangqiu Medical College, Shangqiu, 476000, Henan, People's Republic of China.

出版信息

Arch Gynecol Obstet. 2018 Feb;297(2):433-442. doi: 10.1007/s00404-017-4598-z. Epub 2017 Nov 24.

Abstract

BACKGROUND

The expression of microRNA-21 (miR-21) is up-regulated in various cancers, including cervical cancer. However, the function of miR-21 through tissue inhibitor of metalloproteinase 3 (TIMP3) on the proliferation, migration, and invasion in cervical cancer is still unclear.

METHODS

A total of 60 paired fresh cervical cancer tissues, the corresponding adjacent non-neoplastic tissues and serum samples were collected from cervical cancer patients, while 60 matched normal tissues and serum samples were collected from the control group. MiR-21 expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). TIMP3 expression was evaluated by Western blot and qRT-PCR. Cell proliferation was determined by MTT assay. Migratory and invasive activities were assessed by cell migration and invasion assays, respectively. Luciferase reporter assay was employed to validate the direct targeting of TIMP3 by miR-21.

RESULTS

MiR-21 was up-regulated in cervical cancer tissues and serum samples, in contrast, TIMP3 was down-regulated in cervical cancer tissues. MiR-21 promoted the proliferation, viability and the migratory and invasive activities of cervical cancer cells through targeting TIMP3. Overexpression of TIMP3 attenuated the positive effects of miR-21.

CONCLUSIONS

These findings provide a novel insight into the molecular functions of miR-21 in cervical cancer, which may be used as a diagnostic and prognostic biomarker for the treatment of cervical cancer in the future.

摘要

背景

微小RNA-21(miR-21)在包括宫颈癌在内的多种癌症中表达上调。然而,miR-21通过金属蛋白酶组织抑制剂3(TIMP3)对宫颈癌增殖、迁移和侵袭的作用仍不明确。

方法

收集60对宫颈癌患者的新鲜癌组织、相应的癌旁非肿瘤组织及血清样本,同时收集60例对照组匹配的正常组织及血清样本。采用定量实时聚合酶链反应(qRT-PCR)评估miR-21表达。通过蛋白质免疫印迹法和qRT-PCR评估TIMP3表达。采用MTT法检测细胞增殖。分别通过细胞迁移和侵袭实验评估迁移和侵袭活性。采用荧光素酶报告基因实验验证miR-21对TIMP3的直接靶向作用。

结果

miR-21在宫颈癌组织和血清样本中上调,相反,TIMP3在宫颈癌组织中下调。miR-21通过靶向TIMP3促进宫颈癌细胞的增殖、活力以及迁移和侵袭活性。TIMP3的过表达减弱了miR-21的积极作用。

结论

这些发现为miR-21在宫颈癌中的分子功能提供了新的见解,未来可能用作宫颈癌治疗的诊断和预后生物标志物。

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