A-to-I RNA Editing Endows miR-3664-5p with Carcinogenicity in Breast Cancer Through Modulating LONP2 Mediated Glycolysis

Sep 23, 2026

Breast cancer threatens women’s health, and RNA editing is a key mechanism for altering genetic information. This study investigates the link between A-to-I edited miR-3664-5p and malignant phenotypes in breast cancer. Higher miR-3664-5p editing correlates with tumor stage, recurrence, and patient prognosis. ADAR1 is identified as the key editor. In vitro and mechanistic assays show edited miR-3664-5p acts to promote breast cancer by directly targeting LONP2, regulating PKM2-associated transcription, and modulating glycolysis in vitro and in xenografts.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Introduction

Background on breast cancer

Mechanisms and roles of A-to-I RNA editing

miR-3664-5p evidence in other cancers

Rationale for investigating miR-3664-5p editing and LONP2 in breast cancer

Journal of Mammary Gland Biology and Neoplasia (2026) 31:19 [https://doi.org/10.1007/s1091](https://doi.org/10.1007/s1091) 1-026-09602-1 RESEARCH A-to-I RNA Editing Endows miR-3664-5p with Carcinogenicity in Breast Cancer Through Modulating LONP2 Mediated Glycolysis Yajing Han1 · Xueli Wei1 · Xuesen Zhang1 · Jianjun Wu1 · Fan Wang2 Received: 14 April 2025 / Accepted: 13 February 2026 © The Author(s) 2026 Abstract Breast cancer has become the main cause threatening women’s health. RNA editing is one of the most important mechanisms for modifying genetic information. This study explained the relationship between A-to-I RNA edited miR-3664-5p and malignant phenotype of breast cancer. The results showed that high editing level of miR-3664-5p in breast cancer, which was related to tumor stage, recurrence and prognosis of breast cancer patients. ADAR perturbation experiments demonstrated that ADAR1 is the key enzyme regulating miR-3664-5p editing in breast cancer. A series of in vitro assays revealed that miR-3664-5p functioned as a tumor suppressor in breast cancer, but ed-miR-3664-5p promoted breast cancer development. Mechanically, dual-luciferase reporter assay confirmed that ed-miR-3664-5p directly targets LONP2, yet wt-miR-3664-5p loss this binding site. ChIP assay proved that PKM2 was enriched in the transcriptional regulatory region of LONP2 gene. Seahorse XFe analysis showed that LONP2 knockdown strengthened glycolysis in breast cancer. Xenograft assay also demonstrated that edited miR-3664-5p affected glycolysis in breast cancer through the regulation of LONP2 . In conclusion, A-to-I RNA editing endows miR-3664-5p with carcinogenicity in breast cancer through modulating LONP2 mediated glycolysis. Keywords miR-3664-5p · Breast cancer · A-to-I RNA editing · LONP2 · Glycolysis Introduction As a common malignant tumor of women, breast cancer is the leading cause of death among women [1] . Breast cancer cases in China account for 30% of the world’s total, showing an increasing trend year by year over the past few years [2]. There are many high-risk factors associated with breast cancer, such as heredity and estradiol exposure, but the cause of breast cancer is still unknown [3] . Symptoms of early breast cancer may not be apparent, and patients with terminal breast cancer may suffer from distant metastases, which directly threaten their lives [4] . And the prognosis 􀀍 Fan Wang [zhuge1979wn@163.com](zhuge1979wn@163.com) 1 Breast Surgery, The Fifth People’s Hospital of Datong, Datong, China 2 Breast Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan 030013, China of breast cancer is closely associated with the development stage of the disease. The earlier the disease is discovered, the greater the chance that the patient will live for 5 years [5] . Although breast cancer can be treated with surgery, radiotherapy, chemotherapy, targeted therapy, and hormone therapy, there is a high rate of recurrence following treatment [6]. Thus, exploring the important factors affecting the progress of breast cancer is crucial for early diagnosis and effective treatment. It has become increasingly common for life forms to use RNA editing to modify their genetic code [7] . In precursor mRNA molecules, deamination of adenosine is an important mechanism for RNA editing. A-to-I editing, the deamination event, converts special adenosine into inosine. Translating inosine into guanosine (G) results in codon changes that often result in amino acid substitutions at the amino acid level [8]. Additionally to genetic recoding, A-toI editing can alter alternative splicing, modify microRNAs, and change microRNA targets [9] . In the development of human disease, various A-to-I editing events have occurred. For example, ADAR1 inhibition increases oxidative stress sensitivity of hepatocellular car

FAQs

What is the main focus of the study?

The study focuses on how A-to-I RNA editing affects miR-3664-5p and how this edited microRNA influences breast cancer malignancy.

What does high editing level of miR-3664-5p indicate?

High miR-3664-5p editing level is associated with tumor stage, recurrence, and prognosis of breast cancer patients.

How does edited miR-3664-5p promote breast cancer?

Mechanistically, edited miR-3664-5p directly targets LONP2, and through regulation of LONP2-associated glycolysis—supported by reporter, ChIP, Seahorse, and xenograft assays—it promotes breast cancer development.

Sep 23, 2026

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