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微小RNA-575靶向Derlin 1以调节人甲状腺癌细胞的增殖、迁移和侵袭。

MicroRNA-575 targets Derlin 1 to regulate proliferation, migration and invasion of human thyroid cancer cells.

作者信息

Dong Hong, Wu Yan-Le, Zhang Xin, Li Han-Lin, Zheng Wei-Hong

机构信息

Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Arch Med Sci. 2020 Feb 4;19(4):1108-1115. doi: 10.5114/aoms.2020.92867. eCollection 2023.

Abstract

INTRODUCTION

This study was undertaken to examine the expression of miR-575 in thyroid cancer tissues and to explore its therapeutic potential.

MATERIAL AND METHODS

Expression analysis was carried out by qRT-PCR. The MTT assay was used for cell viability. DAPI and annexin V/PI assays were used to detect apoptosis. Wound healing and Transwell assays were used for cell migration and invasion respectively. Western blot analysis was used to determine the expression of proteins.

RESULTS

The results showed significant downregulation of miR-575 in thyroid cancer tissues and cell lines. The role of miR-575 was deciphered by overexpression of miR-575 in MDA-T32 and MDA-T68 thyroid cancer cells. The results showed that overexpression of miR-575 caused significant inhibition of the proliferation of the MDA-T32 and MDA-T68 cells via induction of apoptotic cell death. The expression of Bax was also enhanced while that of Bax was decreased upon miR-575 overexpression in MDA-T32 and MDA-T68 cells. Additionally, miR-575 overexpression inhibited the migration and invasion of the MDA-T32 and MDA-T68 thyroid cancer cells. Bioinformatic approaches and the dual luciferase assay indicated Derlin 1 (DERL1) to be the potential target of miR-575 in thyroid cancer. DERL1 was significantly upregulated in thyroid cancer tissues and cell lines and overexpression of miR-575 caused suppression of DERL1 in MDA-T68 cells. Silencing of DERL1 inhibited the proliferation of the MDA-T68 cells while overexpression of DERL1 could abolish the effects of miR-575 overexpression on the proliferation of MDA-T68 thyroid cancer cells.

CONCLUSIONS

miR-575 may be used as a therapeutic target for thyroid cancer treatment.

摘要

引言

本研究旨在检测甲状腺癌组织中miR-575的表达,并探索其治疗潜力。

材料与方法

采用qRT-PCR进行表达分析。MTT法用于检测细胞活力。DAPI和膜联蛋白V/PI法用于检测细胞凋亡。伤口愈合实验和Transwell实验分别用于检测细胞迁移和侵袭。蛋白质印迹分析用于测定蛋白质的表达。

结果

结果显示甲状腺癌组织和细胞系中miR-575显著下调。通过在MDA-T32和MDA-T68甲状腺癌细胞中过表达miR-575来解析其作用。结果表明,miR-575过表达通过诱导凋亡性细胞死亡显著抑制MDA-T32和MDA-T68细胞的增殖。在MDA-T32和MDA-T68细胞中,miR-575过表达时Bax的表达增强而Bcl-2的表达降低。此外,miR-575过表达抑制MDA-T32和MDA-T68甲状腺癌细胞的迁移和侵袭。生物信息学方法和双荧光素酶报告基因检测表明Derlin 1(DERL1)是甲状腺癌中miR-575的潜在靶标。DERL1在甲状腺癌组织和细胞系中显著上调,miR-575过表达导致MDA-T68细胞中DERL1受到抑制。沉默DERL1可抑制MDA-T68细胞的增殖,而DERL1过表达可消除miR-575过表达对MDA-T68甲状腺癌细胞增殖的影响。

结论

miR-575可作为甲状腺癌治疗的一个治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e576/10408017/b935b9ff7ecd/AMS-19-4-113011-g001.jpg

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