Promotes Breast Cancer Cell Migration Research Articles

FAK signaling in cancer-associated fibroblasts promotes breast cancer cell migration and metastasis by exosomal miRNAs-mediated intercellular communication.

Cancer-associated fibroblasts (CAFs) are activated fibroblasts that constitute the major components of tumor microenvironment (TME) and play crucial roles in tumor development and metastasis. Here, we generated fibroblast-specific inducible focal adhesion kinase (FAK) knockout (cKO) mice in a breast cancer model to study potential role and mechanisms of FAK signaling in CAF to promote breast cancer metastasis in vivo. While not affecting primary tumor development and growth, FAK deletion significantly suppressed breast cancer metastasis in vivo. Analyses of CAFs derived from cKO mice as well as human CAFs showed that FAK is required for their activity to promote mammary tumor cell migration. We further showed that FAK ablation in CAFs decreased their exosome amount and functions to promote tumor cell migration and other activities, which could contribute to the reduced metastasis observed in cKO mice. Lastly, profiling of miRs from CAF exosomes showed alterations of several exosomal miRs in FAK-null CAFs, and further analysis suggested that miR-16 and miR-148a enriched in exosomes from FAK-null CAFs contribute to the reduced tumor cell activities and metastasis. Together, these results identify a new role for FAK signaling in CAFs that regulate their intercellular communication with tumor cells to promote breast cancer metastasis.

Heterogeneous nuclear ribonucleoprotein A2/B1 is a negative regulator of human breast cancer metastasis by maintaining the balance of multiple genes and pathways.

BackgroundHeterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is an important RNA-binding protein that affects the RNA processing, splicing, transport and stability of many genes. hnRNPA2/B1 is expressed during proliferation and metastasis of various cancer types and promotes such processes. However, the precise role and mechanism of hnRNPA2/B1 in breast cancer remain unclear.MethodsThe association of hnRNPA2/B1 with breast cancer metastasis was assessed using tissue chips, mouse models and publicly available data. The role and mechanism of hnRNPA2/B1 in breast cancer metastasis were studied in cell lines and mouse models.FindingsIn contrast to other cancer research findings, hnRNPA2/B1 expression was negatively correlated with breast cancer metastasis. hnRNPA2/B1 inhibited MDA-MB-231 triple-negative breast cancer (TNBC) cell metastasis in vitro and in vivo. hnRNPA2/B1 knockout activated ERK-MAPK/Twist and GR-beta/TCF4 pathways but inhibited STAT3 and WNT/TCF4 signalling pathways. Profilin 2 (PFN2) promoted breast cancer cell migration and invasion, whereas hnRNPA2/B1 bound directly to the UAGGG locus in the 3′-untranslated region of PFN2 mRNA and reduced the stability of PFN2 mRNA.InterpretationOur data supported the role of hnRNPA2/B1 in tumour metastasis risk and survival prediction in patients with breast cancer. The inhibitory role of hnRNPA2/B1 in metastasis was a balance of downstream multiple genes and signalling pathways. PFN2 downregulation by hnRNPA2/B1 might partly explain the inhibitory mechanism of hnRNPA2/B1 in breast cancer metastasis. Therefore, hnRNPA2/B1 might be used as a new prognostic biomarker and valuable molecular target for breast cancer treatments.

27-Hydroxycholesterol-induced EndMT acts via STAT3 signaling to promote breast cancer cell migration by altering the tumor microenvironment.

Objective: The endothelial to mesenchymal transition (EndMT) plays a major role in cancer metastasis by regulating the complexity of the tumor microenvironment (TME). Here, we investigated whether 27-hydroxycholesterol (27HC) induces EndMT in endothelial cells (ECs).Methods: EndMT markers in the human microvascular endothelial cell-1 (HMEC-1) cell line and human umbilical vein endothelial cells (HUVECs) stimulated with 27HC were evaluated with Western blot. Epithelial to mesenchymal transition (EMT) markers in breast cancer (BC) cells cultured in conditioned medium were investigated with quantitative real time polymerase chain reaction (qRT-PCR). The MMP-2 and MMP-9 mRNA expression and activity were detected with qRT-PCR and gelatin zymography assays, respectively. The effect of activated STAT3 on 27HC-induced EndMT was validated by Western blot, immunofluorescence staining, and cell transfection assays. The migration ability of BC cells was evaluated with Transwell assays.Results: We found that 27HC induced EndMT in HMEC-1 and HUVECs, and 27HC-induced EndMT facilitated EMT and BC cell migration. The 27HC-induced EMT of BC cells also promoted EndMT and HUVEC migration. Investigation of the underlying molecular mechanisms revealed that STAT3 knockdown repressed EndMT in HUVECs as well as migration in BC cells induced with 27HC. In addition, C646 and resveratrol, inhibitors of STAT3 acetylation, repressed the expression of Ac-STAT3, p-STAT3, and EndMT markers in HUVECs exposed to 27HC; these HUVECs in turn attenuated the migration ability of BC cells in 27HC-induced EndMT.Conclusions: Cross-talk between 27HC-induced EndMT and EMT was observed in the TME. Moreover, activation of STAT3 signaling was found to be involved in 27HC-induced EndMT.

MiR-15b facilitates breast cancer progression via repressing tumor suppressor PAQR3.

Recently, breast cancer (BC) has become a common tumor that threatens the physical and mental health of women. Microribonucleic acids (miRNAs) have been chosen as a study object because of their roles in various cancers, including BC. Here, we mainly study the role of miR-15b in BC progression and its underlying mechanism. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the level of MiR-15b expression in 60 pairs of BC tissues and para-cancerous specimens, and the relationship between MiR-15b level and clinical features of BC patient prognosis was analyzed. MiR-15b and PAQR3 level in BC tissues and cells was tested by Western blot. The results showed that miR-15b expression was higher and PAQR3 level was lower in BC. The identification of PAQR3 as a target of miR-15b in BC was carried out by Luciferase reporter assay and the results stated that the Luciferase activity was reduced by miR-15b mimic, indicating PAQR3 being a target of miR-15b in BC. Transwell assay was used for examining BC cell migration and invasion and found that miR-15b could promote BC cell migration and invasion, while the effect of PAQR3 was inhibition. Furthermore, PAQR3 could reverse the promotion effect of miR-15b on BC cell migratory and invasive ability. In addition, miR-15b expression was negatively correlated with PAQR3 performed by regression analysis. Our data stated that miR-15b could facilitate BC progression via repressing tumor suppressor PAQR3, indicating that miR-15b/PAQR3 axis provided a therapeutic target for treating BC.

Long non-coding RNA TTN-AS1 promotes breast cancer cell migration and invasion via sponging miR-140-5p.

Breast cancer (BC) is one of the most common fatal cancers. Recent studies have identified the vital role of long non-coding RNAs (lncRNAs) in the development and progression of BC. In this investigation, lncRNA TTN-AS1 was studied to identify its function in the metastasis of BC. TTN-AS1 expression of tissues was detected by real-time quantitative polymerase chain reaction (RT-qPCR) in 56 BC patients. Wound healing assay and transwell assay were used to observe the biological behavior changes of BC cells through gain or loss of TTN-AS1. In addition, luciferase assays and RNA immunoprecipitation (RIP) assay were performed to discover the potential targets of TTN-AS1 in BC cells. TTN-AS1 expression level in BC samples was higher than that of adjacent tissue. Besides, the ability of cell migration and invasion of BC cells was inhibited after TTN-AS1 was silenced, while cell migration and cell invasion of BC cells were promoted after TTN-AS1 was overexpressed. In addition, miR-140-5p was upregulated after silencing of TTN-AS1 in BC cells, while miR-140-5p was downregulated after overexpression of TTN-AS1 in BC cells. Furthermore, luciferase assays and RIP assay showed that miR-140-5p was a direct target of TTN-AS1 in BC. Our study uncovered a new oncogene in BC and suggests that TTN-AS1 enhances BC cell migration and invasion via sponging miR-140-5p, which provides a novel therapeutic target for BC patients.

Methylation-mediated silencing of miR-133a-3p promotes breast cancer cell migration and stemness via miR-133a-3p/MAML1/DNMT3A positive feedback loop

BackgroundmiR-133a-3p has been recently discovered to be down-regulated in various human malignancies, including breast cancer, and reduced miR-133a-3p levels have been significantly associated with breast cancer cell growth and invasion. However, the regulatory mechanisms leading to abnormal expression of miR-133a-3p in breast cancer remain obscure.MethodsqRT-PCR was applied to detect the expression of miR-133a-3p in breast cancer tissues and cell lines. Bisulfite sequencing was used to detect the degree of methylation of the miR-133a-3p promoter. The effects of miR-133a-3p on breast cancer in vitro were examined by cell proliferation assay, transwell assay, flow cytometry, and western blotting. Bioinformatic analysis, dual-luciferase assay and RIP assay were employed to identify the interaction between miR-133a-3p and MAML1. A xenograft model was used to show the metastasis of breast cancer cells.ResultsWe confirmed that miR-133a-3p was silenced by DNA hypermethylation in breast cancer cell lines and tissues, which predicted poor prognosis in breast cancer patients, and reducing miR-133a-3p expression led to a significant increase in the migration, invasion, proliferation, and stemness of breast cancer cells in vitro. Mastermind-like transcriptional coactivator 1 (MAML1) was confirmed to be a target of miR-133a-3p involved in regulating breast cancer metastasis both in vitro and in vivo. Moreover, a series of investigations indicated that MAML1 initiated a positive feedback loop, which could up-regulate DNA methyltransferase 3A (DNMT3A) to promote hypermethylation of the miR-133a-3p promoter.ConclusionTaken together, our findings revealed a novel miR-133a-3p/MAML1/DNMT3A positive feedback loop in breast cancer cells, which may become a potential therapeutic target for breast cancer.

27-hydroxycholesterol-induced EndMT acts via STAT3 signaling to promote breast cancer cell migration by altering the tumor microenvironment

27-hydroxycholesterol-induced EndMT acts via STAT3 signaling to promote breast cancer cell migration by altering the tumor microenvironment

GPER stabilizes F-actin cytoskeleton and activates TAZ via PLCβ-PKC and Rho/ROCK-LIMK-Cofilin pathway

Actin is a highly abundant cytoskeletal protein that is essential for all eukaryotic cells and participates in many structural and functional roles. It has long been noted that estrogen affects cellular morphology. However, recent studies observed that both estrogen and tamoxifen induce a remarkable cytoskeletal remodeling independent of ER. In addition to ER, G protein-coupled estrogen receptor 1 (GPER, also known as GPR30) also binds to estrogen with high affinity and mediates intracellular estrogenic signaling. Here, we show that activation of GPER by its specific agonist G-1 induces re-organization of F-actin cytoskeleton. We further demonstrate that GPER acts through PLCβ-PKC and Rho/ROCK-LIMK-Cofilin pathway, which are upstream regulators of F-actin cytoskeleton assembly, thereby enhancing TAZ nuclear localization and activation. Furthermore, we find that LIMK1/2 is critical for GPER activation-induced breast cancer cell migration. Together, our results suggest that GPER mediates G-1-induced cytoskeleton assembly and GPER promotes breast cancer cell migration via PLCβ-PKC and Rho/ROCK-LIMK-Cofilin pathway.

ZnR/GPR39 upregulation of K+/Cl−-cotransporter 3 in tamoxifen resistant breast cancer cells

Expression of the zinc receptor, ZnR/GPR39, is increased in higher grade breast cancer tumors and cells. Zinc, its ligand, is accumulated at larger concentrations in the tumor tissue and can therefore activate ZnR/GPR39-dependent Ca2+ signaling leading to tumor progression. The K+/Cl− co-transporters (KCC), activated by intracellular signaling, enhance breast cancer cell migration and invasion. We asked if ZnR/GPR39 enhances breast cancer cell malignancy by activating KCC. Activation of ZnR/GPR39 by Zn2+ upregulated K+/Cl− co-transport activity, measured using NH4+ as a surrogate to K+ while monitoring intracellular pH. Upregulation of NH4+ transport was monitored in tamoxifen resistant cells with functional ZnR/GPR39-dependent Ca2+ signaling but not in MCF-7 cells lacking this response. The NH4+ transport was Na+-independent, and we therefore focused on KCC family members. Silencing of KCC3, but not KCC4, expression abolished Zn2+-dependent K+/Cl− co-transport, suggesting that KCC3 is mediating upregulated NH4+ transport. The ZnR/GPR39-dependent KCC3 activation accelerated scratch closure rate, which was abolished by inhibiting KCC transport with [(DihydroIndenyl) Oxy] Alkanoic acid (DIOA). Importantly, silencing of either ZnR/GPR39 or KCC3 attenuated Zn2+-dependent scratch closure. Thus, a novel link between KCC3 and Zn2+, via ZnR/GPR39, promotes breast cancer cell migration and proliferation.

Long-term cadmium exposure promoted breast cancer cell migration and invasion by up-regulating TGIF

Cadmium (Cd) is a known human carcinogen. Previous studies have demonstrated that Cd exposure promoted migration and invasion of breast cancer cells. However, the molecular mechanisms underlying this process have not yet been clearly addressed. The purpose of this study was to investigate whether TG-interacting factor (TGIF) was involved in long-term Cd exposure-induced migration and invasion of breast cancer cells. Human breast cancer cells were continuously exposed to Cd for eight weeks. Western blot and qRT-PCR assays were performed to measure the expression of protein and mRNA. Migration and invasion assays were performed to assess the migratory and invasive ability of human breast cancer cells. Our data indicated that long-term Cd exposure obviously increased the expression of TGIF protein and mRNA in human breast cancer cells. Long-term Cd exposure increased the ability of migration and invasion of human breast cancer cells, which could be inhibited by transfection of small interfering RNA (siRNA) targeting TGIF. We also observed that the long-term Cd exposure-induced up-regulation of MMP2 mRNA expression was modulated by TGIF. In conclusion, our findings suggested that TGIF/MMP2 signaling axis might be involved in malignant progression stimulated by long-term Cd exposure in human breast cancer.

Nrf2 promotes breast cancer cell migration via up-regulation of G6PD/HIF-1α/Notch1 axis.

Abnormal metabolism of tumour cells is closely related to the occurrence and development of breast cancer, during which the expression of NF‐E2‐related factor 2 (Nrf2) is of great significance. Metastatic breast cancer is one of the most common causes of cancer death worldwide; however, the molecular mechanism underlying breast cancer metastasis remains unknown. In this study, we found that the overexpression of Nrf2 promoted proliferation and migration of breast cancers cells. Inhibition of Nrf2 and overexpression of Kelch‐like ECH‐associated protein 1 (Keap1) reduced the expression of glucose‐6‐phosphate dehydrogenase (G6PD) and transketolase of pentose phosphate pathway, and overexpression of Nrf2 and knockdown of Keap1 had opposite effects. Our results further showed that the overexpression of Nrf2 promoted the expression of G6PD and Hypoxia‐inducing factor 1α (HIF‐1α) in MCF‐7 and MDA‐MB‐231 cells. Overexpression of Nrf2 up‐regulated the expression of Notch1 via G6PD/HIF‐1α pathway. Notch signalling pathway affected the proliferation of breast cancer by affecting its downstream gene HES‐1, and regulated the migration of breast cancer cells by affecting the expression of EMT pathway. The results suggest that Nrf2 is a potential molecular target for the treatment of breast cancer and targeting Notch1 signalling pathway may provide a promising strategy for the treatment of Nrf2‐driven breast cancer metastasis.

A novel PAK4-CEBPB-CLDN4 axis involving in breast cancer cell migration and invasion

Claudin-4 (CLDN4), a crucial member of tight junction proteins, is aberrantly expressed in breast cancer cells and contributes to cell migration and invasion. However, the mechanisms controlling CLDN4 expression in breast cancer are poorly understood. Here, we reported that CLDN4 expression correlated positively with p21-activated kinase 4 (PAK4) expression in human breast cancer tissues. Knockdown of PAK4 in MDA-MB-231 and ZR-75-30 cells suppressed CLDN4 expression and significantly inhibited cell migration and invasion. Conversely, restoration of CLDN4 expression in PAK4-knockdown cells reversed the inhibition of migration and invasion. We identified CCAAT/enhancer-binding protein β (CEBPB) as a novel transcriptional regulator of CLDN4 and confirmed that CEBPB bound to the −1093 to −991 bp region of the CLDN4 promoter. Importantly, we found that PAK4 enhanced CEBPB phosphorylation on Thr-235. In summary, we showed that PAK4-mediated CEBPB activation upregulated CLDN4 expression to promote breast cancer cell migration and invasion. Our results might contribute to understanding the mechanisms of CLDN4 regulation and suggest PAK4-CEBPB-CLDN4 axis as a potential therapeutic target for breast cancer.

Abstract P6-05-08: LINC02273 interacts with hnRNPL and promotes metastasis through directly activating AGR2 in breast cancer

Abstract The prognosis of breast cancer patients with metastasis is still poor even improved by current treatment modalities. Unveiling new biomarkers and molecular mechanisms that underlie metastasis are of vital importance for the treatment of breast cancer. The recent discovery of long noncoding RNAs (lncRNAs) has gained widespread attention. To identify critical lncRNAs that contributed to breast cancer metastasis, we profiled their expression in 5 pairs of primary tumors and lymph nodes metastasis loci by HTA2.0 microarray. LINC02273 is significantly upregulated in metastasis loci and its high expression is associated with poor diseases free survival in a validation set of 254 patients. LINC02273 was mainly located in the cell nucleus . RACE-PCR showed two isoforms and the longest one was the most abundant isoform in breast cancer. Through transwell assay, 3D spheroid invasion assay and mice xenograft metastasis model, we found that LINC02273 promoted breast cancer cell migration, invasion and metastasis. Via mass spectrometry, hnRNPL was found to interact with LINC02273 to enhance its stability, which was further confirmed by Actinomycin D inhibition assay and luciferase reporter assay. Furthermore, ChIRP-seq and ChIP-seq showed that LINC02273 stimulated oncogene AGR2 expression by directly binding to the AGR2 promoter region and increasing H3K27ac modification. Triplex formation assay was performed for verification. We demonstrated that the expression level and oncogenic ability of AGR2 were regulated by hnRNPL through LINC02273. Clinical data and mouse xenograft tumors also revealed the positive correlation of AGR2 and LINC02273. In conclusion, LINC02273, which is stabilized by hnRNPL can promote breast cancer metastasis through upregulation of AGR2 and may serve as a prognostic biomarker for breast cancer. Citation Format: Xiu B, Chi Y, Ji W, Zhang Q, Wu J. LINC02273 interacts with hnRNPL and promotes metastasis through directly activating AGR2 in breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-05-08.

Co-culture With Human Breast Adipocytes Differentially Regulates Protein Abundance in Breast Cancer Cells.

Recent research highlights the role of cancer-associated adipocytes (CAA) in promoting breast cancer cell migration, invasion and resistance to therapy. This study aimed at identifying cellular proteins differentially regulated in breast cancer cells co-cultured with CAA. Adipocytes isolated from human breast adipose tissue were co-cultured with hormone receptor-positive (MCF-7) or -negative (MDA-MB-231) breast cancer cells using a transwell co-culture system. Proteomes of co-cultured and control breast cancer cells were compared quantitatively using iTRAQ labelling and tandem mass spectrometry, and the results were validated by western blotting. A total of 1,126 and 1,218 proteins were identified in MCF-7 and MDA-MB-231 cells, respectively. Among these, 85 (MCF-7) and 63 (MDA-MB-231) had an average fold change >1.5 following co-culture. Pathway analysis revealed that CAA-induced enrichment of proteins involved in metabolism, the ubiquitin proteasome, and purine synthesis. This study provides a proteomic platform for investigating the paracrine role of CAA in promoting breast cancer cell metastasis and resistance to therapy.

Sonic Hedgehog stimulates migration of MCF-7 breast cancer cells through Rac1

As one of the most common tumors in women, breast cancer has drawn considerable interest from investigators and clinicians in recent years. Despite early diagnosis and best therapeutic regimens available, the prognosis of malignant or metastatic breast cancer patients is still not optimistic. Hedgehog signaling, a classical pathway indispensable to embryonic development, participates in the growth of a variety of tumors. In the present study, the effect of Sonic Hedgehog (Shh) on breast cancer cells was investigated. We identified that Shh signal stimulated the migration of MCF-7 breast cancer cells. Smo and Gli1 were involved in Shh-stimulated migration of MCF-7 cells. Activating Smo and Gli1 induced cell migration, which was blocked by their specific antagonists. The effect of Shh signaling on MCF-7 cells was independent of Wnt5a, Dvl2 and Rab35, but directly dependent on Rac1. In conclusion, our study suggested that Shh promotes breast cancer cell migration <i>via</i> Rac1 independently of the non-canonical Wnt signaling pathway, which may represent a rational molecular target for combination medication in breast cancer.

CUL1 promotes breast cancer metastasis through regulating EZH2-induced the autocrine expression of the cytokines CXCL8 and IL11

CUL1 is an essential component of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex. Our previous study has showed that CUL1 is positively associated with poor overall and disease-specific survival of breast cancer patients. Here, we further explored its roles in breast cancer metastasis. Our data showed that CUL1 significantly promoted breast cancer cell migration, invasion, tube formation in vitro, as well as angiogenesis and metastasis in vivo. In mechanism, the human gene expression profiling was used to determine global transcriptional changes in MDA-MB-231 cells, and we identified autocrine expression of the cytokines CXCL8 and IL11 as the target genes of CUL1 in breast cancer cell migration, invasion, metastasis, and angiogenesis. CUL1 regulated EZH2 expression to promote the production of cytokines, and finally significantly aggravating the breast cancer cell metastasis and angiogenesis through the PI3K–AKT–mTOR signaling pathway. Combined with the previous report about CUL1, we proposed that CUL1 may serve as a promising therapeutic target for breast cancer metastasis.

Retraction: Mitochondrial Dysfunction Promotes Breast Cancer Cell Migration and Invasion through HIF1α Accumulation via Increased Production of Reactive Oxygen Species.

Retraction: Mitochondrial Dysfunction Promotes Breast Cancer Cell Migration and Invasion through HIF1α Accumulation via Increased Production of Reactive Oxygen Species.

Cathepsin D enhances breast cancer invasion and metastasis through promoting hepsin ubiquitin-proteasome degradation

Hepsin is required for the growth and maintenance of normal morphology, as well as for cell motility and development, initiation of blood coagulation and pro-inflammatory immune response. Here we showed that Cathepsin D (CtsD) as a novel protein is involved in the regulation of hepsin. CtsD destabilizes hepsin by promoting its ubiquitylation and subsequent proteasomal degradation in breast cancer cells. Breast cancer tissue microarray also indicated that hepsin expression was negatively correlated with CtsD by immunohistochemistry. Overexpression of CtsD promoted breast cancer cell migration, invasion and metastasis by enhancing the expression of intercellular cell adhesion molecule-1 (ICAM-1) in vitro and in vivo. These effects were inhibited by ectopic hepsin expression. Taken together, our data reveal a critical CtsD-hepsin signaling axis in migration and metastasis, which may contribute to a better understanding of the function and molecular mechanism in breast cancer progression.

Overexpression of CXCR4 synergizes with LL-37 in the metastasis of breast cancer cells

Chemokine receptor CXCR4 was involved in the progression of breast cancer to a metastatic phenotype, leading to the major cause of death in patients. A more in-depth understanding of signaling mechanism underlying CXCR4 is critical to develop effective therapies toward metastasis. Recently, the role of antimicrobial peptide LL-37 in contributing to the metastasis of breast cancer cells was observed. Clinical analysis of data herein demonstrated for the first time that overexpression of LL-37 and CXCR4 co-existed in human primary breast tumors with lymph node metastases. Further study disclosed that forced expression of CXCR4 led to the enhancement of pro-migratory signaling and migration rate induced by LL-37 in breast cancer cells. Moreover, LL-37 affected tumor microenvironment including induction of migration of mesenchymal stem cells and CXCR4-dependent capillary-like tubule formation. Functional analysis showed that LL-37 induced the internalization of CXCR4 through approaching Glu268, the residue of CXCR4, independent of the binding pocket (Asp171, Asp262, and Glu288) for CXCR4 inhibitor AMD3100, signifying that LL-37 is a distinct agonist of CXCR4. These results suggest the reciprocal roles of LL-37 and CXCR4 in promoting breast cancer cell migration and provide new insight into the design of CXCR4 inhibitor for intervention of metastatic breast cancer.

Circular RNA hsa_circ_0072995 promotes breast cancer cell migration and invasion through sponge for miR-30c-2-3p.

To study the role of hsa_circ_0072995 in regulating the invasion and migration of breast cancer cells. Hsa_circ_0072995 expression was confirmed by quantitative real-time PCR; evaluating the migration and invasion of breast cancer cells through transwell assay; predicating circRNA/microRNAs interaction using the miRanda and RNAhybrid software; identifying the relationship between hsa_circ_0072995 and miR-30c-2-3p by luciferase activity assay; detecting the location of hsa_circ_0072995 by Fluorescence in situ hybridization assay. Hsa_circ_0072995 was significantly upregulated in MDA-MB-231 cells compared with MCF-7 cells. Hsa_circ_0072995 regulated the invasion and migration of breast cancer cells. Hsa_circ_0072995 existed in the nucleus and cytoplasm, and the proportion of the two was roughly equal. Hsa_circ_0072995 bound to miR-30c-2-3p. Overexpression of miR-30c-2-3p inhibited breast cancer cells migration and invasion. Low expression of miR-30c-2-3p was correlated with poor overall survival by The Cancer Genome Atlas database. Hsa_circ_0072995 may be a novel biomarker for breast cancer, and may function in metastasis of breast cancer.