miR-29a contributes to breast cancer cells epithelial-mesenchymal transition, migration, and invasion via down-regulating histone H4K20 trimethylation through directly targeting SUV420H2.

Cell Death & Disease
You WuLiang Jin

Abstract

Breast cancer is the most prevalent cancer in women worldwide, which remains incurable once metastatic. Breast cancer stem cells (BCSCs) are a small subset of breast cancer cells which are essential in tumor formation, metastasis, and drug resistance. microRNAs (miRNAs) play important roles in the breast cancer cells and BCSCs by regulating specific genes. In this study, we found that miR-29a was up-regulated in BCSCs, in aggressive breast cancer cell line and in breast cancer tissues. We also confirmed suppressor of variegation 4-20 homolog 2 (SUV420H2), which is a histone methyltransferase that specifically trimethylates Lys-20 of histone H4 (H4K20), as the target of miR-29a. Both miR-29a overexpression and SUV420H2 knockdown in breast cancer cells promoted their migration and invasion in vitro and in vivo. Furthermore, we discovered that SUV420H2-targeting miR-29a attenuated the repression of connective tissue growth factor (CTGF) and growth response protein-1 (EGR1) by H4K20 trimethylation and promoted the EMT progress of breast cancer cells. Taken together, our findings reveal that miR-29a plays critical roles in the EMT and metastasis of breast cancer cells through targeting SUV420H2. These findings may provide new insigh...Continue Reading

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Citations

Jul 28, 2019·International Journal of Molecular Sciences·Xinping LiYi Pan
Jan 8, 2020·Cancers·Carla Solé, Charles H Lawrie
Jul 17, 2020·Non-coding RNA·Jun Sheng Wong, Yoke Kqueen Cheah
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Oct 2, 2021·Frontiers in Cell and Developmental Biology·Wei LiDa Pang

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Methods Mentioned

BETA
flow cytometry
transfection
confocal microscopy
immunoprecipitation
ChIP
xenografts

Software Mentioned

HISAT2
HTSEQ
Stringtie
BD FACS Diva
Genergy
miRanda
PicTar
TargetScan
EdgeR
GraphPad Prism

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