A Feedback Loop Between LncRNA MALAT1 and DNMT1 Promotes Triple-negative Breast Cancer Stemness and Tumorigenesis

Overview

Journal Cancer Biol Ther

Specialties Oncology
Pharmacology

Date 2023 Aug 7

PMID 37548553

Authors

Yu Hu

Yuqiong He

Na Luo

Xin Li

Lei Guo

Kejing Zhang

Affiliations

Soon will be listed here.

Abstract

Background: The function of long non-coding RNA (lncRNA) MALAT1 in regulating triple-negative breast cancer (TNBC) stemness and tumorigenesis was investigated.

Methods: Sphere formation and colony formation assays coupled with flow cytometry were employed to evaluate the percentage of CD44/CD44 cells, and ALDH cells were performed to evaluate the stemness. Bisulfite sequencing PCR (BSP) was employed to detect the methylation level of MALAT1. Tumor xenograft experiment was performed to evaluate tumorigenesis . Finally, dual-luciferase reporter and RIP assays were employed to verify the binding relationship between MALAT1 and miR-137.

Results: Our results revealed that MALAT1 and BCL11A were highly expressed in TNBC, while miR-137 and DNMT1 were lowly expressed. Our results proved that MALAT1 positively regulated BCL11A expression through targeting miR-137. Functional experiments revealed that MALAT1 inhibited DNMT1 expression through acting on the miR-137/BCL11A pathway to enhance TNBC stemness and tumorigenesis. We also found that high MALAT1 expression in TNBC was related to the DNMT1-mediated hypomethylation of MALAT1. As expected, DNMT1 overexpression could remarkably inhibit TNBC stemness and tumorigenesis, which was eliminated by MALAT1 overexpression.

Conclusion: MALAT1 downregulated DNMT1 by miR-137/BCL11A pathway to enhance TNBC stemness and tumorigenesis; meanwhile, DNMT1/MALAT1 formed a positive feedback loop to continuously promote TNBC malignant behaviors.

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