Impact of miR-193a-3p on migration and invasion of breast cancer stem cells through targeting TRIM14

Xinrong WANG; Peixian WANG; Haiqing REN; Huan WANG

doi:10.19401/j.cnki.1007-3639.2025.11.002

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Impact of miR-193a-3p on migration and invasion of breast cancer stem cells through targeting TRIM14

Article | 更新时间：2025-12-31

- Impact of miR-193a-3p on migration and invasion of breast cancer stem cells through targeting TRIM14
- China Oncology Vol. 35, Issue 11, Pages: 1001-1009(2025)
- 作者机构：
  
  邢台市人民医院检验科，河北邢台 054000
- 作者简介：
- 基金信息：
  
  2025 Hebei Provincial Medical Science Research Project Plan(20251412)
- DOI：10.19401/j.cnki.1007-3639.2025.11.002
  CLC： R737.9
- Received：14 May 2025，
  
  Revised：2025-09-07，
  
  Published：30 November 2025
- 稿件说明：
移动端阅览
Xinrong WANG, Peixian WANG, Haiqing REN, et al. Impact of miR-193a-3p on migration and invasion of breast cancer stem cells through targeting TRIM14[J]. China Oncology, 2025, 35(11): 1001-1009.
DOI：

Xinrong WANG, Peixian WANG, Haiqing REN, et al. Impact of miR-193a-3p on migration and invasion of breast cancer stem cells through targeting TRIM14[J]. China Oncology, 2025, 35(11): 1001-1009. DOI： 10.19401/j.cnki.1007-3639.2025.11.002.

摘要

背景和目的：

乳腺癌干细胞在癌症的发生、发展中发挥重要作用，乳腺癌患者死亡率较高与癌症的复发及转移密切相关，然而乳腺癌干细胞的自我更新和分化能力能够引发化疗耐药性，进而影响肿瘤的复发和转移。本研究旨在探究miR-193a-3p通过靶向三结构域蛋白14（tripartite motif-containing protein 14，TRIM14）对乳腺癌干细胞迁移和侵袭的影响。

方法：

选择人乳腺癌细胞T47D作为研究对象，随机分组分为Control组、NC mimics组（转染NC mimics）、miR-193a-3p mimics组（转染miR-193a-3p mimics）、miR-193a-3p mimics＋pcDNA-NC组（转染miR-193a-3p mimics+pcDNA-NC）和miR

-193a-3p mimics＋pcDNA-TRIM14组（转染miR-193a-3p mimics+pcDNA-TRIM14）。采用流式细胞术分离干细胞并检测细胞成球能力；通过细胞计数试剂盒-8（cell counting kit-8，CCK-8）实验检测细胞增殖；使用transwell实验检测细胞迁移和侵袭；通过流式细胞术检测细胞凋亡率；采用蛋白质印迹法（Western blot）检测细胞中细胞周期蛋白D1（cyclin D1）、基质金属蛋白酶-2（matrix metalloproteinase-2，MMP-2）、Bcl-2相关X蛋白（Bcl-2-associated X protein，Bax）及TRIM14蛋白的表达；采用双萤光素酶报告基因实验检测miR-193a-3p与TRIM14的相互作用。

结果：

T47D干细胞具有成球能力，并随着时间推移增强，T47D干细胞球体积逐渐增大。与Control组、NC mimics组相比，miR-193a-3p mimics组细胞miR-193a-3p表达、凋亡率、Bax蛋白表达升高（

0.05），TRIM14 mRNA和蛋白表达、存活率、克隆数、迁移数、侵袭数、cyclin D1、MMP-2降低（

0.05）。与miR-193a-3p mimics组、miR-193a-3p mimics＋pcDNA-NC组相比，miR-193a-3p mimics＋pcDNA-TRIM14组细胞凋亡率、Bax蛋白表达降低（

0.05），TRIM14 mRNA和蛋白表达、存活率、克隆数、迁移数、侵袭数、cyclin D1、MMP-2升高（

0.05）。miR-193a-3p与TRIM14之间存在多个结合位点。与miR-NC＋TRIM14-WT组相比，miR-193a-3p mimics＋TRIM14-WT组双萤光素酶活性明显降低（

0.05）。

结论：

miR-193a-3p可能通过抑制TRIM14表达，发挥抑制乳腺癌干细胞迁移和侵袭的作用。

Abstract

Background and purpose:

Breast cancer stem cells play an important role in the occurrence and development of cancer. The high mortality of breast cancer patients is closely related to the recurrence and metastasis of cancer. However

the self-renewal and differentiation ability of breast cancer stem cells can lead to chemotherapy resistance

thus affecting the recurrence and metastasis of cancer. This study aimed to explore the impact of miR-193a-3p on the migration and invasion of breast cancer stem cells by targeting the tripartite motif-containing protein 14 (TRIM14).

Methods:

Human breast cancer cell T47D was randomly assigned into control group

NC mimics group (transfected with NC mimics)

miR-193a-3p mimics group (transfected with miR-193a-3p mimics)

miR-193a-3p mimics+pcDNA-NC group (transfected with miR-193a-3p mimics+pcDNA-NC) and miR-193a-3p mimics+pcDNA-TRIM14 group (transfected with miR-193a-3p mimics+pcDNA-TRIM14). Separation of stem cells usin

g flow cytometry and detection of cell spheroidization ability were carried out. Cell counting kit-8 (CCK-8) experiment was used to detect cell proliferation. Transwell experiment was used to measure cell migration and invasion. Flow cytometry was used to detect cell apoptotic rate. Western blot was used to detect the expressions of cyclin D1

matrix metalloproteinase-2 (MMP-2)

Bcl-2-associated X protein (Bax)

and TRIM14 protein in cells. Dual luciferase assay was used to detect the interaction between miR-193a-3p and TRIM14.

Results:

T47D stem cells had the ability to form spheroids

and with increasing time

the spheroid volume of T47D stem cells gradually increased. Compared with the Control group and NC mimics group

the miR-193a-3p mimics group showed increased miR-193a-3p expression

apoptotic rate

and Bax protein expression (

0.05)

and decreased TRIM14 mRNA and protein expression

survival rate

clone number

migration number

invasion number

cyclin D1 and MMP-2 (

0.05). Compared with the miR-193a-3p mimics group and the miR-193a-3p mimics+pcDNA NC group

the miR-193a-3p mimics+pcDNA-TRIM14 group showed decreased cell apoptosis rate and Bax protein (

0.05)

and increased TRIM14 mRNA and protein expression

survival rate

clone number

migration number

invasion number

cyclin D1 and MMP-2 (

0.05). There were multiple binding sites between miR-193a-3p and TRIM14. Compared with the miR-NC+TRIM14-WT group

the miR-193a-3p mimics+TRIM14-WT group showed a prominent decrease in dual luciferase activity (

0.05).

Conclusion:

MiR-193a-3p may inhibit the migration and invasion of breast cancer stem cells through inhibiting TRIM14.

关键词

Keywords

references

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