|Table of Contents|

METTL3-mediated m6A modification of CCNE1 regulates the sensitivity of breast cancer cells to palbociclib

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 05
Page:
787-791
Research Field:
Publishing date:

Info

Title:
METTL3-mediated m6A modification of CCNE1 regulates the sensitivity of breast cancer cells to palbociclib
Author(s):
HOU Lan1; 2; DAI Yinhai3; WANG Zhe2; JIAO Yangchi2; CHANG Kexin2; WANG Mao3; WU Shaofeng3; QI Jing3; ZHANG Juliang2
1.The Second Clinical School of Medicine,Shaanxi University of Chinese Medicine,Shaanxi Xianyang 712000,China;2.Department of Thyroid,Breast and Vascular Surgery,the First Affiliated Hospital of Air Force Medical University,Shaanxi Xi'an 710032,China;3.Department of Cancer Breast Surgery,the Second Affiliated Hospital of Shaanxi University of Chinese Medicine,Shaanxi Xianyang 712000,China.
Keywords:
breast cancer; METTL3; CCNE1; palbociclib; sensitivity
PACS:
R737.9
DOI:
10.3969/j.issn.1672-4992.2024.05.001
Abstract:
Objective:To investigate the effect of m6A modification mediated by RNA methyltransferase METTL3 on the palbociclib sensitivity of breast cancer cells and to explore its underlying mechanism.Methods:Breast cancer cell line MCF-7 were randomly divided into si-NC group,si-METTL3 group,si-CCNE1 group,si-METTL3+OE-NC group and si-METTL3+OE-CCNE1 group.The mRNA and protein expression levels of METTL3 and CCNE1 were detected by qPCR and Western blot,respectively.The sensitivity of palbociclib was detected by CCK-8 assay.The interaction of METTL3 and CCNE1 mRNA was detected by RIP experiment.The m6A modification level of CCNE1 was detected by MeRIP-qPCR.The stability of CCNE1 mRNA was detected by adding actinomycin D.Results:The mRNA levels of METTL3 and CCNE1 were significantly increased in MCF-7 cells(P＜0.05).Inhibition of METTL3 or CCNE1 expression significantly increased the sensitivity of palbociclib in MCF-7 cells(P＜0.05),and inhibition of METTL3 significantly decreased the mRNA and protein expression levels of CCNE1(P＜0.05).RIP experiments confirmed the interaction between METTL3 and CCNE1 mRNA,and CCNE1 was modified by m6A.Compared with the si-NC group,the m6A modification level of CCNE1 in the si-METTL3 group was significantly reduced,and the stability of CCNE1 mRNA was significantly decreased.Further experiments showed that the palbociclib sensitivity in si-METTL3+OE-CCNE1 group was significantly lower than that in si-METTL3+OE-NC group(P＜0.05).Conclusion:The expression of METTL3 and CCNE1 was up-regulated in MCF-7 cells.METTL3 inhibition improved the sensitivity of MCF-7 cells to pipercilil,which was related to the regulation of CCNE1 mRNA stability by METTL3-mediated m6A modification.

References:

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Memo

Memo:
National Natural Science Foundation of China（No.81902677）;国家自然科学基金青年基金项目(编号：81902677)；陕西省重点研发计划(编号：2018ZDXM-SF-066)
Last Update: 2024-01-30