BHLHE41 suppresses MCF‐7 cell invasion via MAPK/JNK pathway

Abstract

| 4001 wileyonlinelibrary.com/journal/jcmm | INTRODUC TI ONBasic helix-loop-helix family member e41 (BHLHE41, also known as SHARP1, DEC2 and BHLHB3) is mapped to human chromosome 12p12.1. It serves an important role in regulating cell differentiation, maintaining circadian rhythm, apoptosis, hypoxia and immune response. [1][2][3][4][5][6][7][8][9][10][11] The major functions of BHLHE41 are divided into two categories: circadian and non-circadian regulation. For the former, BHLHE41 protein re-enters the nucleus after transcription and translation and competes with CLOCK-BMAL1 heterodimer for E-Box element binding (through competitive inhibition). BHLHE41 functions as a suppressor of circadian rhythm regulation in this process. 11,12 For non-circadian regulation, BHLHE41 is implicated in multiple other pathways, such as BCR, notch, hypoxia, ERK/NF-kappaB and PI3K/Akt pathways. 3,6,8,[13][14][15] Dysregulation of BHLHE41 transcription levels has been characterized as a marker of the progression of several cancers. 8,[16][17][18][19][20][21][22][23] Abstract Deregulation of the basic helix-loop-helix family member e41 (BHLHE41) has been characterized as a marker of progression of several cancers. In this study, we aimed to explore the mechanism by which BHLHE41 regulates the invasion of breast cancer cells. BHLHE41 suppresses, whereas the silencing of BHLHE41 promotes tumour invasion of both MCF-7 and MDA-MB-231 cells. Meanwhile, BHLHE41 down-regulated the transcription and translation of SNAI1, SNAI2, VIM and CDH2, and up-regulated those of CLDN1, CLDN4 and CDH1. Reporter assay indicated that silencing of BHLHE41 dramatically activated the MAPK/JNK signalling pathway in MCF-7 cell line and the hypoxia signalling pathway in MDA-MB-231 cell line. Furthermore, silencing of BHLHE41 activated the MAPK/JNK signalling pathway by up-regulating phosphorylated JNK and failed to affect the expression of HIF-1 alpha in MCF-7 cells. After blocking the MAPK/JNK signalling pathway by specific inhibitor SP600125, silencing of BHLHE41 failed to promote tumour cell invasion. These results suggest that BHLHE41 facilitates MCF-7 cell invasion mainly via the activation of MAPK/ JNK signalling pathway. In conclusion, although BHLHE41 suppresses tumour invasion in MCF-7 and MDA-MB-231 cell lines, the specific regulatory mechanisms may be different. K E Y W O R D S BHLHE41, breast cancer, invasion, JNK signalling pathway, tight junction How to cite this article: Zhang D, Zheng Q, Wang C, Zhao N, Liu Y, Wang E. BHLHE41 suppresses MCF-7 cell invasion via MAPK/JNK pathway.

Fusobacterium nucleatum Promotes Gastric Cancer Aggressiveness through Upregulation of Cell Mobility and Interferon Genes

“…Among these genes are NR1D1 [5,18], [3,37], and PER1 [14], which participate in circadian molecular mechanism but are implicated in cancer progression as well. It is possible that suppression of these genes and activation of actins and other cell adhesion genes are done through a common Fusobacterium nucleatum-dependent regulation mechanism.…”

M1A and m7G modification-related genes are potential biomarkers for survival prognosis and for deciphering the tumor immune microenvironment in esophageal squamous cell carcinoma

“…The sextet of pivotal genes (BHLHE41, C12orf65, CHD7, LAMP5, RPA1, SLC2A4RG) serve as fundamental players in prognosticating ESCC, each of them has been highlighted in preceding research concerning diverse types of malignancies. Dysregulation of BHLHE41, a gene implicated in tumor progression, has been substantiated within the context of breast and colorectal cancers [ 56 , 57 ]. Additionally, mutations in C12orf65 have been postulated to engender carcinogenic consequences through perturbations in mitochondrial functionality [ 58 ].…”

NRBP1 negatively regulates SALL4 to reduce the invasion and migration, promote apoptosis and increase the sensitivity to chemotherapy drugs of breast cancer cells

“…Estrogen receptor-positive cell line MCF-7 was selected in the present experiments and multiple reports have investigated the mechanism underlying the malignant progression of BC by detecting proliferation, migration and invasion of the MCF-7 cell line ( 18 – 20 ).…”

“…There were several limitations in the present study. Multiple reports have investigated the mechanism of malignant progression of breast cancer by detecting proliferation, migration and invasion of the MCF-7 cell line ( 18 – 20 ). Thus, the focus was primarily on the phenotype of ER-positive cell line MCF-7, which is also one of the limitations of the paper.…”