EPAS1 targeting by miR-152-3p in Paclitaxel-resistant Breast Cancer

Abstract

Background: Paclitaxel plays a pivotal role in the chemotherapy of breast cancer, but resistance to this drug is an important obstacle in the treatment. It is reported that microRNA-152-3p (miR-152-3p) is involved in tamoxifen resistance in breast cancer, but whether it is involved in paclitaxel resistance in breast cancer remains unknown. Materials and methods: We examined the expression of miR-152-3p in breast cancer tissues and cells by qRT-PCR. After transfecting paclitaxel-resistant MCF-7/TAX cells with miR-152-3p mimics, we analyzed the function of miR-152-3p in these cells by MTT assay and flow cytometry. We screened the target gene, endothelial PAS domain-containing protein 1 (EPAS1), using bioinformatics analysis and verified it with the dual luciferase reporter gene experiment. The relationship between EPAS1 and miR-152-3p and their roles in paclitaxel resistance of breast cancer were further investigated using RNA interference and transfection techniques. Results: The expression of miR-152-3p in normal breast tissues and cells was markedly higher than that in breast cancer. Overexpression of miR-152-3p decreased the survival rate and increased the apoptosis rate and sensitivity of MCF-7/TAX cells to paclitaxel. We confirmed that EPAS1 is the target of miR-152-3p and is negatively regulated by this miRNA. Moreover, transfection with EPAS1 siRNA enhanced the susceptibility and apoptosis rate of MCF-7/TAX cells to paclitaxel. Co-transfection of miR-152-3p mimics and EPAS1 increased paclitaxel sensitivity and apoptosis induced by the drug. Conclusion: miR-152-3p inhibits the survival of MCF-7/TAX cells and promotes their apoptosis by targeting the expression of EPAS1, thereby, enhancing the sensitivity of these breast cancer cells to paclitaxel.

Hsa_circRNA_102229 facilitates the progression of triple‐negative breast cancer via regulating the miR‐152‐3p/PFTK1 pathway

“…41 miR-152-3p and PFTK1 were selected as downstream molecules of hsa_circ_102229 based on studies showing that miR-152-3p and PFTK1 are associated with breast cancer. 42,43 In the present study, PFTK1 was confirmed as a direct target of miR-152-3p. In line with the previous results of above studies, overexpression of PFTK1 could compromise the inhibitory effects of hsa_circ_102229, suggesting that hsa_circ_102229 could promote the proliferation, migration and invasion of TNBC cells by regulating PFTK1.…”

Development of an Oxidative Phosphorylation-Related and Immune Microenvironment Prognostic Signature in Uterine Corpus Endometrial Carcinoma

“…Based on the 289 OXPHOS-related gene matrix obtained from the research of Zihao Xu, we used differential expression analysis and identified 66 OXPHOS-related DEGs, including 54 upregulated genes and 12 downregulated genes; most of them have been reported to be associated with cancer. For instance, EPAS1 could enhance the effect of paclitaxel on breast cancer cells by inhibiting growth and promoting apoptosis of MCF-7/TAX cells ( Song et al, 2020 ). Furthermore, functional annotation of the OXPHOS-related DEGs also indicated that the candidate genes were significantly related to ATP metabolic process, purine ribonucleoside triphosphate metabolic process, and the essential pathways reported in many cancers ( Matsuda et al, 2017 ; Fallah and Rini, 2019 ), including retrograde endocannabinoid signaling and HIF-1 signaling pathways.…”

microRNA152-3p protects against ischemia/reperfusion-induced BBB destruction possibly targeting MAP3K2/JNK/c-Jun pathway

“…Hence protecting endothelial cells can maintain the integrity of BBB. The function of miR-152-3p to modulate apoptosis in cancers has been well established [29,30]. Recent years, the anti-apoptotic effect of miR-152-3p in injury diseases have received increasing investment.…”