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Updated: Jul 23, 2025

miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
METTL3-mediated m6A modification of pri-miR-148a-3p affects prostate cancer progression by regulating TXNIP
Guoqiang Li1, Junwen Liu2, Yinhuai Wang1
1Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, China.
Objective:
Prostate cancer (PCa) severely affects men's health worldwide. The mechanism of methyltransferase-like 3 (METTL3) in affecting PCa development by regulating miR-148a-3p expression via N6-methyladenosine (m6A) modification was investigated.
Methods:
METTL3, miR-148a-3p, and thioredoxin interacting protein (TXNIP) levels were determined using RT-qPCR and Western blotting. The m6A modification level of miR-148a-3p was observed by Me-RIP assay. Bioinformatics website predicted miR-148a-3p and TXNIP levels in PCa and their correlation, and the binding site between them was verified by dual-luciferase assay. The proliferation, migration, invasion, and apoptosis of PCa cells were examined by CCK-8 assay, Transwell assay, and flow cytometry. A transplanted tumor model was established in nude mice to observe the tumor growth ability, followed by determination of TXNIP levels in tumor tissues by immunohistochemistry.
Results:
METTL3 interference restrained the proliferation, migration, and invasion and promoted apoptosis of PCa cells. METTL3 up-regulated miR-148a-3p by promoting the m6A modification of pri-miR-148a-3p in PCa cells. miR-148a-3p overexpression nullified the inhibitory actions of silencing METTL3 on PCa cell growth. miR-148a-3p facilitated PCa cell growth by silencing TXNIP. METTL3 interference inhibited tumor growth by down-regulating miR-148a-3p and up-regulating TXNIP.
Conclusion:
METTL3 promoted miR-148a-3p by mediating the m6A modification of pri-miR-148a-3p, thereby targeting TXNIP, interfering with METTL3 to inhibit the proliferation, migration and invasion of PCa cells, promote apoptosis, and inhibit tumor growth in nude mice.
Insights
Methyltransferase-like 3 (METTL3) promotes prostate cancer (PCa) by upregulating miR-148a-3p via m6A modification, which silences TXNIP. Interfering with METTL3 inhibits PCa progression and tumor growth.
Area of Science:
- Molecular Oncology
- Epigenetics
- RNA Modifications
Background:
- Prostate cancer (PCa) is a significant global health concern for men.
- The role of methyltransferase-like 3 (METTL3) in PCa pathogenesis requires elucidation.
- N6-methyladenosine (m6A) modification is increasingly recognized for its role in cancer.
Purpose of the Study:
- To investigate the mechanism by which METTL3 influences PCa development.
- To determine the regulatory relationship between METTL3, miR-148a-3p, and TXNIP in PCa.
- To explore the potential of targeting the METTL3/miR-148a-3p/TXNIP axis for PCa therapy.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) and Western blotting assessed gene and protein expression.
- Me-RIP assay quantified m6A modification levels of pri-miR-148a-3p.
- In vitro (cell-based assays) and in vivo (xenograft mouse models) experiments evaluated PCa cell behavior and tumor growth.
Main Results:
- METTL3 interference suppressed PCa cell proliferation, migration, and invasion, while promoting apoptosis.
- METTL3 upregulated miR-148a-3p expression through m6A modification of pri-miR-148a-3p.
- miR-148a-3p overexpression reversed the inhibitory effects of METTL3 silencing; miR-148a-3p silenced TXNIP, promoting PCa cell growth.
Conclusions:
- METTL3 promotes PCa progression by enhancing miR-148a-3p via m6A modification, leading to TXNIP downregulation.
- Targeting METTL3 effectively inhibits PCa cell proliferation, migration, invasion, and tumor growth in vivo.
- The METTL3/miR-148a-3p/TXNIP pathway represents a potential therapeutic target for prostate cancer.
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