miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer

Abstract

MicroRNAs (miRNAs) have critical roles in regulating cancer cell survival, proliferation and sensitivity to chemotherapy. The potential application of using miRNAs to predict chemotherapeutic response to cancer treatment is highly promising. However, the underlying mechanisms of chemotherapy response control by miRNAs remain to be fully identified and their prognostic value has not been fully evaluated. Here we show a strong correlation between miR-205 expression and chemosensitivtiy to TAC (docetaxol, doxorubicin plus cyclophosphamide), a widely-used neoadjuvant chemotherapy (NAC) regimen, for breast cancer patients. High level of miR-205 predicted better response to TAC regimen NAC in breast cancer patients. We found miR-205 downregulated in both MCF-7/A02 and CALDOX cells, two drug-resistant derivatives of MCF-7 and Cal51 cells, and its ectopic expression led to an increase in apoptosis resensitization of both drug-resistant cell lines to doxorubicin and taxol. We further show that miR-205 directly binds VEGFA and FGF2 mRNA 3′-UTRs and confirm that miR-205 levels are negatively correlated with VEGFA and FGF2 mRNA expression in breast cancer patients. Adding VEGFA and FGF2 exogenously to chemosensitive breast cancer cells and chemoresistant cells with miR-205 overexpression led to drug resistance. Consistently, low VEGFA and FGF2 expression correlated with better response to NAC in breast cancer patients. In addition, inhibition of tumor growth and resensitization to doxorubicin were also observed in mouse tumor xenografts from cells overexpressing miR-205. Taken together, our data suggest that miR-205 enhances chemosensitivity of breast cancer cells to TAC chemotherapy by suppressing both VEGFA and FGF2, leading to evasion of apoptosis. MiR-205 may serve as a predictive biomarker and a potential therapeutic target in breast cancer treatment.

Decreased expression of microRNA-17 and microRNA-20b promotes breast cancer resistance to taxol therapy by upregulation of NCOA3

“…20 Moreover, recent study reports that miRNA-205 enhances breast cancer cell resistance to doxorubicin and taxol by targeting VEGFA and FGF2. 21 …”

MiR‐205 promotes endothelial progenitor cell angiogenesis and deep vein thrombosis recanalization and resolution by targeting PTEN to regulate Akt/autophagy pathway and MMP2 expression

“…Our previous studies have demonstrated that miRNAs have a vital role in EPC function . Additionally, miR‐205 has been shown to have different effects on angiogenesis and migration in different types of tumours . Meanwhile, miR‐205 promotes wound healing in human corneal epithelial cells .…”

“…11,[27][28][29][30] Additionally, miR-205 has been shown to have different effects on angiogenesis and migration in different types of tumours. [32][33][34][35]42 Meanwhile, miR-205 promotes wound healing in human corneal epithelial cells. 31 However, the role and underlying mechanism of miR-205 in DVT and EPCs, particularly in regulating angiogenesis and thrombus resolution, remain to be elucidated.…”

Identification and Verification of Candidate Genes Regulating Neural Stem Cells Behavior Under Hypoxia

“…Subsequently, we performed a search in PubMed for these 14 miRNAs and found that 7 of them had been confirmed experimentally to target VEGFA, that is, miR-361 [40, 41], miR-140 [42], miR-15a [43], miR-15b [44], miR-205 [45], miR-206 [46], and miR-200c [47]. Therefore, we speculate that these miRNAs may target VEGFA and play a role in NSC behavior under hypoxia.…”