MiR-27a-5p inhibits malignant progression of differentiated thyroid cancer by directly affecting the miR-27a-5p/SREBP1 axis.

IF 3.5 2区 医学 Q1 Medicine Journal of Endocrinological Investigation Pub Date : 2025-06-01 Epub Date: 2025-02-13 DOI:10.1007/s40618-025-02550-3
Zilan Xie, Jianqiu Liu, Jiating Zhou, Xuan Zhang, Zhi Li
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Abstract

Purpose: To detect the expression of miR-27a-5p in differentiated thyroid cancer (DTC) and to explore its correlation with SREBP1 expression, DTC malignant progression, and TSH suppression therapy.

Methods: The expression levels of SREBP1 and miR-27a-5p in DTC tissues (n = 75) were detected by qRT-PCR. The expression of miR-27a-5p and SREBP1 was statistically analyzed for correlation with patients' postoperative TSH inhibition therapy. Dual luciferase reporter gene assay was performed to verify the target-regulatory relationship between miR-27a-5p and SREBP1. qRT-PCR and Western blots were performed to detect the effect of miR-27a-5p on the expression level of SREBP1. MTS, plate clone formation assay was performed to detect the effect of miR-27a-5p on the proliferative capacity of cells. Flow cytometry was performed to detect the effect of miR-27a-5p on cell cycle and apoptosis. Scratch assay and Transwell assay was performed to detect the effect of miR-27a-5p on cell migration invasion ability.

Results: MiR-27a-5p expression was significantly downregulated in DTC cancer tissues and significantly negatively correlated with SREBP1 expression. It correlated with the outcome of postoperative TSH suppression therapy in DTC patients. The results of dual luciferase reporter gene assay showed that the 3'-UTR region of SREBP1 mRNA was the target site of action of miR-27a-5p. Overexpression of miR-27a-5p was associated with a significant reduction in cell proliferation, cell cycle arrest, increased apoptosis, and diminished cell invasive migration.

Conclusion: The miR-27a-5p expression level was negatively correlated with the progression of DTC, which may be inhibited by targeting SREBP1 and correlated with the outcome of TSH inhibitory therapy.

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MiR-27a-5p通过直接影响MiR-27a-5p /SREBP1轴抑制分化型甲状腺癌的恶性进展。
目的:检测miR-27a-5p在分化型甲状腺癌(DTC)中的表达,并探讨其与SREBP1表达、DTC恶性进展及TSH抑制治疗的相关性。方法:采用qRT-PCR检测75例DTC组织中SREBP1和miR-27a-5p的表达水平。统计学分析miR-27a-5p和SREBP1的表达与患者术后TSH抑制治疗的相关性。双荧光素酶报告基因检测验证miR-27a-5p与SREBP1之间的靶调控关系。采用qRT-PCR和Western blots检测miR-27a-5p对SREBP1表达水平的影响。MTS,板克隆形成实验检测miR-27a-5p对细胞增殖能力的影响。流式细胞术检测miR-27a-5p对细胞周期和凋亡的影响。采用Scratch法和Transwell法检测miR-27a-5p对细胞迁移侵袭能力的影响。结果:MiR-27a-5p在DTC癌组织中表达显著下调,与SREBP1表达呈显著负相关。它与DTC患者术后TSH抑制治疗的结果相关。双荧光素酶报告基因检测结果显示,SREBP1 mRNA的3'-UTR区域是miR-27a-5p的作用靶点。过表达miR-27a-5p与细胞增殖显著降低、细胞周期阻滞、细胞凋亡增加和细胞侵袭性迁移减少相关。结论:miR-27a-5p表达水平与DTC的进展呈负相关,可能通过靶向SREBP1抑制DTC的进展,并与TSH抑制治疗的结果相关。
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来源期刊
Journal of Endocrinological Investigation
Journal of Endocrinological Investigation ENDOCRINOLOGY & METABOLISM-
CiteScore
8.10
自引率
7.40%
发文量
242
期刊介绍: The Journal of Endocrinological Investigation is a well-established, e-only endocrine journal founded 36 years ago in 1978. It is the official journal of the Italian Society of Endocrinology (SIE), established in 1964. Other Italian societies in the endocrinology and metabolism field are affiliated to the journal: Italian Society of Andrology and Sexual Medicine, Italian Society of Obesity, Italian Society of Pediatric Endocrinology and Diabetology, Clinical Endocrinologists’ Association, Thyroid Association, Endocrine Surgical Units Association, Italian Society of Pharmacology.
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