FTO-regulated m6A modification of pri-miR-139 represses papillary thyroid carcinoma metastasis.
10.11817/j.issn.1672-7347.2025.250018
- Author:
Jiale LI
1
,
2
;
Ping ZHOU
1
;
Juan DU
3
;
Hongwei SHEN
4
;
Yongfeng ZHAO
1
;
Shanshan YU
5
Author Information
1. Department of Ultrasound, Third Xiangya Hospital, Central South University, Changsha
2. 198302052@csu.edu.cn.
3. Department of Breast and Thyroid Surgery, Third Xiangya Hospital, Central South University, Changsha
4. Department of Medical Experiment Center, Second Xiangya Hospital, Central South University, Changsha
5. Department of Information Network Center, Third Xiangya Hospital, Central South University, Changsha 410013, China. yushanshan1218@sina.com.
- Publication Type:Journal Article
- Keywords:
N 6-methyladenosine modification;
bioinformatics analysis;
fat mass and obesity-associated protein;
m 6 A target microRNAs;
papillary thyroid carcinoma;
serum circulating microRNAs
- MeSH:
Humans;
MicroRNAs/metabolism*;
Thyroid Cancer, Papillary/metabolism*;
Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism*;
Thyroid Neoplasms/metabolism*;
Cell Line, Tumor;
Neoplasm Metastasis;
Adenosine/genetics*;
Gene Expression Regulation, Neoplastic;
Female;
Male;
Cadherins/metabolism*;
Cell Proliferation;
Zinc Finger E-box-Binding Homeobox 1/genetics*
- From:
Journal of Central South University(Medical Sciences)
2025;50(5):815-826
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:Increasing detection of low-risk papillary thyroid carcinoma (PTC) is associated with overdiagnosis and overtreatment. N6-methyladenosine (m6A)-mediated microRNA (miRNA) dysregulation plays a critical role in tumor metastasis and progression. However, the functional role of m6A-miRNAs in PTC remains unclear. This study aims to elucidate the regulatory mechanism of m6A-miR-139-5p expression in PTC, determine its association with PTC metastasis, and evaluate its potential as a diagnostic biomarker for PTC metastasis, thereby providing experimental evidence for precision diagnosis and therapy.
METHODS:Expression profiles of m6A-miRNAs were compared between the The Cancer Genome Atlas (TCGA) and GSE130512 cohorts to identify metastasis-associated candidates. Clinical specimens from 13 metastasis and 18 non-metastasis PTC patients were analyzed to assess m6A-miR-139-5p expression and its correlation with metastasis. Functional experiments were conducted to investigate the effect of fat mass and obesity-associated protein (FTO) on pri-miR-139 methylation and processing, clarifying its regulatory role in miR-139-5p expression. In TPC-1 cells, MTT assays were performed to evaluate whether miR-139-5p overexpression could counteract FTO-mediated cell proliferation. Transwell invasion assays were used to determine the impact of miR-139-5p on PTC cell invasion, exploring whether it functions through the ZEB1/E-cadherin axis.
RESULTS:By comparing TCGA and GSE130512 cohorts, it was found that circulating m6A-miR-139-5p could serve as a biological indicator for detecting PTC metastasis. Detection of 13 metastatic and 18 non-metastatic clinical specimens showed that FTO inhibited the processing of pri-miR-139 by reducing its methylation level, leading to the dysregulation of miR-139-5p in PTC (P<0.05). In TPC-1 cells, MTT assay showed that overexpression of miR-139-5p could partially reverse FTO overexpression-mediated cell proliferation (P<0.05). In addition, miR-139-5p inhibited the invasive ability of PTC cells by targeting the ZEB1/E-cadherin axis, while FTO overexpression could partially weaken this inhibitory effect.
CONCLUSIONS:Circulating miR-139-5p can be a potential marker for evaluating PTC metastasis. FTO affects the expression and function of miR-139-5p by regulating m6A modification of pri-miR-139, but its clinical value needs further verification.
