Eribulin upregulates miR-195 expression and downregulates Wnt3a expression in non-basal-like type of triple-negative breast cancer cell MDA-MB-231

Abstract

Triple-negative breast cancer (TNBC), which does not show hormone sensitivity, is a poor prognosis disease without an established targeted treatment, so that establishing a therapeutic target for each subtype is desired. In addition, microRNA (miRNA), a non-cording RNA 19-25 nucleotide-longs in length, is known to be involved in regulating gene expression. We examined miRNA expression after exposure to eribulin, MDA-MB-231 cells, non-basal-like type of TNBC cell lines, and HCC1143 cells, basal-like type of TNBC cell lines. The activity of caspase-3 significantly increased compared to the control in MDA-MB-231, whereas no significant difference was observed in HCC1143. The expression level of 20-miRNAs significantly increased compared to the control in MDA-MB-231 after exposure to eribulin. The expression level of 6-miRNAs also significantly increased compared to the control in HCC1143. In these 2 cell types, miR-125b-1 and miR-195 were commonly expressed. While the expression level of miR-125b-1 decreased in both cells, the expression level of miR-195 increased in MDA-MB-231 and decreased in HCC1143. The expression level of miR-195 targeting Wnt3a significantly decreased compared to the control in MDA-MB-231, whereas it significantly increased in HCC1143. These results showed that exposure to eribulin highly increased the expression of miR-195 while it decreased the expression of Wnt3a in non-basal-like type of TNBC. Some miRNAs are known to regulate other signaling pathways involved in human pathogenesis by regulating the Wnt signaling pathway, and miRNA can act as a tumor-suppressing gene; therefore, miR-195 may serve as a therapeutic target in non-basal-like type of TNBC.

RETRACTED ARTICLE: miR-195-5p/NOTCH2-mediated EMT modulates IL-4 secretion in colorectal cancer to affect M2-like TAM polarization

“…miR-195-5p is a member of evolutionarily conserved miRNAs termed the miR-15/107 family which has been suggested to have considerable potential in prognostic prediction [33–35]. miR-195-5p acts as a tumor suppressor in tumor progression by targeting numerous genes, such as YAP1 in CRC [29], RPS6KB1 in prostate cancer [35], MMP14 in cervical carcinoma [36], and NOTCH2 in osteosarcoma [12].…”

MicroRNA-195: a review of its role in cancers

“… 166 Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer characterized by the absence of estrogen, progesterone and HER-2 receptor expression, accounting for approximately 12%–17% of breast cancer cases, having a poor prognosis, and accompanied by a high risk of recurrence. 167 Furuya et al 168 reported that eribulin treatment strongly increases miR-195 levels in a non-basal-like type of TNBC cell line, MDA-MB-231, 168 and miR-195 was reported to downregulate Wnt3a in the same work.…”

Clinical Value of miR-101-3p and Biological Analysis of its Prospective Targets in Breast Cancer: A Study Based on The Cancer Genome Atlas (TCGA) and Bioinformatics

“…The chemokine signaling pathway mediates chemokines and promotes the chemotaxis, growth, and survival of BC cells [42]. miR-195 suppressed the Wnt signaling pathway, which promotes cell proliferation and the metastasis of TNBC [43]. Han et al reported that the ErbB signaling pathway can be regulated by STAT1 in the tumorigenesis of BC [44].…”