Paeoniflorin Sensitizes Breast Cancer Cells to Tamoxifen by Downregulating microRNA-15b via the FOXO1/CCND1/β-Catenin Axis

Abstract

Background: Paeoniflorin (Pae) possesses anti-tumor activity in various malignancies. However, it is unclear whether Pae plays a sensitizer role in breast cancer (BC) and the molecular mechanisms involved in this process. Our oligonucleotide microarray revealed that microRNA (miR)-15b is the most significantly downregulated miRNA in MCF-7/ 4-hydroxytamoxifen (4-OHT) cells treated with Pae. This paper summarized the relevance of Pae in BC cell endocrine resistance to tamoxifen (Tam) and the molecular mechanisms involved miR-15b expression. Materials and Methods: 4-OHT-resistant BC cell lines were developed and treated with different concentrations of Pae. Flow cytometry, lactose dehydrogenase activity, caspase-3 activity, colony formation, and EdU assays were carried out to assess the impact of Pae on BC cells. Differentially expressed miRNAs in BC cells treated with Pae were analyzed by microarray. Targeting mRNAs of screened miR-15b as well as the binding of forkhead box O1 (FOXO1) to the cyclin D1 (CCND1) promoter sequence were predicted through bioinformatics analysis. Finally, the expression of β-catenin signaling-related genes in cells was detected by Western blotting. Results: Pae (100 μg/mL) inhibited the clonality and viability of BC cells, while enhancing apoptosis in vitro. Pae also repressed miR-15b expression. Overexpression of miR-15b restored the growth and resistance of BC cells to 4-OHT. Moreover, Pae promoted FOXO1 expression by downregulating miR-15b, thereby transcriptionally inhibiting CCND1 and subsequently blocking β-catenin signaling. Conclusion: Pae inhibits 4-OHT resistance in BC cells by regulating the miR-15b/FOXO1/ CCND1/β-catenin pathway.

Integrated Bioinformatics and Experimental Analysis Identified TRIM28 a Potential Prognostic Biomarker and Correlated with Immune Infiltrates in Liver Hepatocellular Carcinoma

“…So, we hypothesize that TRIM28 is linked to immune cell infiltration and significantly promotes tumor progression in LIHC. The hypothesis is in accordance with the results of these past studies [ 11 – 14 ].…”

LDHA deficiency inhibits trophoblast proliferation via the PI3K/AKT/FOXO1/CyclinD1 signaling pathway in unexplained recurrent spontaneous abortion

“…35 The transcription factor FOXO1 binds to the CyclinD1 promoter sequence to influence gene expression. 36 Accumulating studies have reported that FOXO1 plays an important role in early placental development and is involved in early pregnancy loss. 37,38 Under oxidative stress, FOXO1-mediated trophoblast integrin β3 expression could be impaired.…”

Identification of hub genes for early detection of bone metastasis in breast cancer

“…Globally, among all women, the most frequently detected and diagnosed and the most lethal type of cancer is breast cancer (BC) (1). Distant metastasis and drug resistance represent the major causes of death in patients with BC (2)(3)(4)(5)(6). In particular, bone is one of the most frequent distant metastases in BC patients and bone metastasis arises in approximately 80% of advanced BC patients (7).…”

“…Hoxa5microrna-26a-5p promotes osteosarcoma cell proliferation and migration by targeting in vitro and in vivo ( 10 ). Previous literature suggests that, both in vitro and in vivo , paeoniflorin regulates the migration and invasion of breast cancer cells by down-regulating microrNA-15B through FOXO1/CCND1/β-catenin axis ( 6 ). Previous studies have also indicated that CEP55 was a key regulator in BC spinal metastases by Bioinformatics Analyses ( 11 ).…”