BMAL1 Knockdown Leans Epithelial–Mesenchymal Balance toward Epithelial Properties and Decreases the Chemoresistance of Colon Carcinoma Cells

Autor: Julien Giron-Michel, Annabelle Ballesta, Hervé Acloque, Christophe Desterke, Eva Hadadi, Yao Xiang, Aurore Devocelle, Lucas Eduardo Botelho de Souza, Yunhua Chang, Yuan Zhang, Adlen Foudi
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Colorectal cancer
Vimentin
Keratin-20
Metastasis
Small hairpin RNA
Cell Movement
Databases
Genetic
circadian clock
Biology (General)
epithelial–mesenchymal transition (EMT)
beta Catenin
Spectroscopy
Gene knockdown
biology
ARNTL Transcription Factors
chemoresistance
General Medicine
Cadherins
Epithelial Cell Adhesion Molecule
Computer Science Applications
Oxaliplatin
Protein Transport
Chemistry
Gene Knockdown Techniques
Colonic Neoplasms
endocrine system
Epithelial-Mesenchymal Transition
Cell Survival
QH301-705.5
colorectal cancer
Article
Catalysis
Inorganic Chemistry
Antigens
CD
Cell Line
Tumor
medicine
Humans
metastasis
Neoplasm Invasiveness
Physical and Theoretical Chemistry
QD1-999
Molecular Biology
neoplasms
Cell Membrane
Organic Chemistry
Mesenchymal stem cell
BMAL1
Cancer
Epithelial Cells
medicine.disease
digestive system diseases
Drug Resistance
Neoplasm
Cell culture
biology.protein
Cancer research
Cell Adhesion Molecules
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 10
International Journal of Molecular Sciences, Vol 22, Iss 5247, p 5247 (2021)
ISSN: 1422-0067
DOI: 10.3390/ijms22105247
Popis: The circadian clock coordinates biological and physiological functions to day/night cycles. The perturbation of the circadian clock increases cancer risk and affects cancer progression. Here, we studied how BMAL1 knockdown (BMAL1-KD) by shRNA affects the epithelial–mesenchymal transition (EMT), a critical early event in the invasion and metastasis of colorectal carcinoma (CRC). In corresponding to a gene set enrichment analysis, which showed a significant enrichment of EMT and invasive signatures in BMAL1_high CRC patients as compared to BMAL1_low CRC patients, our results revealed that BMAL1 is implicated in keeping the epithelial–mesenchymal equilibrium of CRC cells and influences their capacity of adhesion, migration, invasion, and chemoresistance. Firstly, BMAL1-KD increased the expression of epithelial markers (E-cadherin, CK-20, and EpCAM) but decreased the expression of Twist and mesenchymal markers (N-cadherin and vimentin) in CRC cell lines. Finally, the molecular alterations after BMAL1-KD promoted mesenchymal-to-epithelial transition-like changes mostly appeared in two primary CRC cell lines (i.e., HCT116 and SW480) compared to the metastatic cell line SW620. As a consequence, migration/invasion and drug resistance capacities decreased in HCT116 and SW480 BMAL1-KD cells. Together, BMAL1-KD alerts the delicate equilibrium between epithelial and mesenchymal properties of CRC cell lines, which revealed the crucial role of BMAL1 in EMT-related CRC metastasis and chemoresistance.
Databáze: OpenAIRE
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