Simultaneous detection of breast cancer biomarkers circROBO1 and BRCA1 based on a CRISPR-Cas13a/Cas12a system.

Breast cancer is reported to be one of the most lethal cancers in women, and its multi-target detection can help improve the accuracy of diagnosis. In this work, a cluster regularly interspaced short palindromic repeats (CRISPR)-Cas13a/Cas12a-based system was established for the simultaneous fluorescence detection of breast cancer biomarkers circROBO1 and BRCA1. CRISPR-Cas13a and CRISPR-Cas12a were directly activated by their respective targets, resulting in the cleavage of short RNA and DNA reporters, respectively, thus the signals of 6-carboxyfluorescein (FAM) and 6-carboxy-xrhodamine (ROX) were restored. As the fluorescence intensities of FAM and ROX were dependent on the concentrations of circROBO1 and BRCA1, respectively, synchronous fluorescence scanning could achieve one-step detection of circROBO1 and BRCA1 with detection limits of 0.013 pM and 0.26 pM, respectively. The system was highly sensitive and specific, holding high diagnostic potential for the detection of clinical samples. Furthermore, the competing endogenous RNA mechanism between circROBO1 and BRCA1 was also explored, providing a reliable basis for the intrinsic regulatory mechanism of breast cancer.

Causal relationship between immune cells and prostate cancer: a Mendelian randomization study.

Introduction: Despite the abundance of research indicating the participation of immune cells in prostate cancer development, establishing a definitive cause-and-effect relationship has proven to be a difficult undertaking. Methods: This study employs Mendelian randomization (MR), leveraging genetic variables related to immune cells from publicly available genome-wide association studies (GWAS), to investigate this association. The primary analytical method used in this study is inverse variance weighting (IVW) analysis. Comprehensive sensitivity analyses were conducted to assess the heterogeneity and horizontal pleiotropy of the results. Results: The study identifies four immune cell traits as causally contributing to prostate cancer risk, including CD127- CD8+ T cell %CD8+ T cell (OR = 1.0042, 95%CI:1.0011-1.0073, p = 0.0077), CD45RA on CD39+ resting CD4 regulatory T cell (OR = 1.0029, 95%CI:1.0008-1.0050, p = 0.0065), CD62L- Dendritic Cell Absolute Count (OR = 1.0016; 95%CI:1.0005-1.0026; p = 0.0039), CX3CR1 on CD14+ CD16- monocyte (OR = 1.0024, 95%CI:1.0007-1.0040, p = 0.0060). Additionally, two immune cell traits are identified as causally protective factors: CD4 on monocyte (OR = 0.9975, 95%CI:0.9958-0.9992, p = 0.0047), FSC-A on plasmacytoid Dendritic Cell (OR = 0.9983, 95%CI:0.9970-0.9995, p = 0.0070). Sensitivity analyses indicated no horizontal pleiotropy. Discussion: Our MR study provide evidence for a causal relationship between immune cells and prostate cancer, holding implications for clinical diagnosis and treatment.

Methylation of GPRC5A promotes liver metastasis and docetaxel resistance through activating mTOR signaling pathway in triple negative breast cancer.

AIMS: This study aims to explore the function and mechanism of G Protein-coupled receptor class C group 5 member A (GPRC5A) in docetaxel-resistance and liver metastasis of breast cancer. METHODS: Single-cell RNA transcriptomic analysis and bioinformatic analysis are used to screen relevant genes in breast cancer metastatic hepatic specimens. MeRIP, dual-luciferase analysis and bioinformation were used to detect m6A modulation. Mass spectrometry (MS), co-inmunoprecipitation (co-IP) and immunofluorescence colocalization were executed to explore the mechanism of GPRC5A in breast cancer cells. RESULT: GPRC5A was upregulated in triple-negative breast cancer (TNBC) and was associated with a poor prognosis. In vitro and in vivo experiments demonstrated that knockdown of GPRC5A alleviated metastasis and resistance to docetaxel in TNBC. Overexpression of GPRC5A had the opposite effects. The m6A methylation of GPRC5A mRNA was modulated by METTL3 and YTHDF1, which facilitates its translation. GPRC5A inhibited the ubiquitination-dependent degradation of LAMTOR1, resulting in the recruitment of mTORC1 to lysosomes and activating the mTORC1/p70s6k signaling pathway. CONCLUSION: METTL3/YTHDF1 axis up-regulates GPRC5A expression by m6A methylation. GPRC5A activates mTORC1/p70s6k signaling pathway by recruiting mTORC1 to lysosomes, consequently promotes docetaxel-resistance and liver metastasis.

JAK/STAT in leukemia: a clinical update.

Over the past three decades, considerable efforts have been expended on understanding the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in leukemia, following the identification of the JAK2V617F mutation in myeloproliferative neoplasms (MPNs). The aim of this review is to summarize the latest progress in our understanding of the involvement of the JAK/STAT signaling pathway in the development of leukemia. We also attempt to provide insights into the current use of JAK/STAT inhibitors in leukemia therapy and explore pertinent clinical trials in this field.

UCP2 promotes NSCLC proliferation and glycolysis via the mTOR/HIF-1α signaling.

BACKGROUND: Metabolic disturbance is a hallmark of cancers. Targeting key metabolic pathways and metabolism-related molecular could be a potential therapeutic approach. Uncoupling protein 2 (UCP2) plays a pivotal part in the malignancy of cancer and its capacity to develop resistance to pharmaceutical interventions. However, it is unclear about the mechanism of how UCP2 acts in the tumor growth and metabolic reprogramming process in non-small cell lung cancer (NSCLC). METHODS: Here, we conducted qRT-PCR to investigate the expression of UCP2 in both NSCLC tissues and cell lines. Subsequent functional studies including colony formation assay, CCK-8 assay, and glycolysis assay were conducted to investigate the functions of UCP2 in NSCLC. The regulatory mechanism of UCP2 toward the mammalian target of rapamycin (mTOR) and hypoxia-inducible factor-1 alpha (HIF-1α) signaling in NSCLC was confirmed through western blotting. RESULTS: We observed a significant upregulation of UCP2 in both NSCLC tissues and cell lines. The increased expression of UCP2 has a strong association with a worse outlook. Silencing UCP2 remarkably dampened NSCLC cell proliferation and glycolysis capacities. Mechanically, UCP2 promoted NSCLC tumorigenesis partially via regulating the mTOR/HIF-1α axis. CONCLUSION: Taken together, we explored the functions as well as the mechanisms of the UCP2/mTOR/HIF-1α axis in NSCLC progression, uncovering potential biological signatures and targets for NSCLC treatment.

Non-alcoholic fatty liver disease promotes breast cancer progression through upregulated hepatic fibroblast growth factor 21.

Non-alcoholic fatty liver disease (NAFLD) has been shown to influence breast cancer progression, but the underlying mechanisms remain unclear. In this study, we investigated the impact of NAFLD on breast cancer tumor growth and cell viability through the potential mediator, hepatic fibroblast growth factor 21 (FGF21). Both peritumoral and systemic administration of FGF21 promoted breast cancer tumor growth, while FGF21 knockout attenuated the tumor-promoting effects of the high-fat diet. Mechanistically, exogenous FGF21 treatment enhanced the anti-apoptotic ability of breast cancer cells through STAT3 and Akt/FoXO1 signaling pathways, and mitigated doxorubicin-induced cell death. Furthermore, we observed overexpression of FGF21 in tumor tissues from breast cancer patients, which was associated with poor prognosis. These findings suggest a novel role for FGF21 as an upregulated mediator in the context of NAFLD, promoting breast cancer development and highlighting its potential as a therapeutic target for cancer treatment.

Tumor-derived Exosomal ENO2 Modulates Polarization of Tumor-associated Macrophages through Reprogramming Glycolysis to Promote Progression of Diffuse Large B-cell Lymphoma.

Macrophages can be polarized into functional classically activated (M1) or alternatively activated (M2) phenotype. Tumor-associated macrophages (TAMs) mainly exhibit M2 phenotype. Previous works determined that up-regulation of enolase 2 (ENO2) in diffuse large B-cell lymphoma (DLBCL) cells can promote macrophages to an M2-like phenotype, thereby consequently promoting the progression of DLBCL. Exosomes are a subset of extracellular vesicles, carrying various bioactive molecules, mediate signals transduction and regulate immune cells. In our study, we investigated the role and related mechanisms of DLBCL-derived exosomal ENO2 in regulating macrophage polarization during DLBCL progression via bioinformatics analysis and a series of experiments. The results of bioinformatics analysis indicated that high expression of ENO2 was positively correlated with DLBCL progression and macrophages M2/M1 ratio. ENO2 protein levels were increased in the exosomes of the sera of DLBCL patients and DLBCL cells. Moreover, the DLBCL-derived exosomes were assimilated by macrophages and then regulated macrophage polarization. The results of in vitro and in vivo experiments showed that DLBCL-derived exosomal ENO2 modulated macrophages polarization (increased M2 phenotype and decreased M1 phenotype), thereby promoting DLBCL proliferation, migration, and invasion. We then revealed that the modulation of macrophages polarization by DLBCL-derived exosomal ENO2 depended on glycolysis and was promoted through GSK3ß/ß-catenin/c-Myc signaling pathway. These findings suggested that DLBCL-derived exosomal ENO2 accelerated glycolysis via GSK3ß/ß-catenin/c-Myc signaling pathway to ultimately promote macrophages to an M2-like phenotype, which can promote the proliferation, migration and invasion of DLBCL, suggesting that exosomal ENO2 may be a promising therapeutic target and prognostic biomarker for DLBCL.

A novel axis of circKIF4A-miR-637-STAT3 promotes brain metastasis in triple-negative breast cancer.

Among patients with triple-negative breast cancer (TNBC), distant metastasis is the leading cause of death. Our previous studies have shown that TNBC progression is greatly facilitated by circKIF4A, but uncertainty remains regarding its role in TNBC brain metastasis and the molecular mechanism. In this study, we found notable upregulation of circKIF4A in TNBC cell lines and brain metastases. Inhibition of circKIF4A impaired the ability of TNBC to proliferate, migrate, and cause brain metastasis. Luciferase reporter assays confirmed that circKIF4A competed for binding to miR-637 with STAT3 3' UTR. Western blot analysis revealed that inhibition of circKIF4A decreased STAT3 and p62 expression, while increased the LC3B-II/LC3B-I ratio and the expression of Beclin, indicating that downregulation of circKIF4A induced autophagy by competing with STAT3 for binding to miR-637. By employing a competitive endogenous RNA (ceRNA) mechanism, the circKIF4A-miR-637-STAT3 axis coordinates brain metastasis in TNBC. circKIF4A can therefore be used as a prognostic biomarker for brain metastasis in TNBC and as a therapeutic target.

circROBO1 promotes prostate cancer growth and enzalutamide resistance via accelerating glycolysis.

Background and aim: As non-coding RNAs, circular RNAs (circRNAs) contribute to the progression of malignancies by regulating various biological processes. In prostate cancer, however, there is still a lack of understanding regarding the potential molecular pathways and roles of circRNAs. Methods: Loss-off function experiments were performed to investigate the potential biological function of circRNA in the progression of prostate cancer. Western blot, qRT-PCR, and IHC assay were used to examine the expression level of different genes or circRNAs. Further molecular biology experiments were conducted to uncover the molecular mechanism underlying circRNA in prostate cancer using dual luciferase reporter and RNA immunoprecipitation (RIP) assays. Results: A novel circRNA (hsa_circ_0124696, named circROBO1) was identified as a significantly upregulated circRNA in both prostate cancer cells and tissues. Suppression of circROBO1 significantly attenuated the proliferation of prostate cancer cells. In addition, we found that the knockdown of circROBO1 remarkably increased the sensitivity of prostate cancer to enzalutamide treatment. A deceleration in glycolysis rate was observed after inhibition of circROBO1, which could suppress prostate cancer growth and overcome resistance to enzalutamide. Our results revealed that circROBO1 promotes prostate cancer growth and enzalutamide resistance via accelerating glycolysis. Conclusion: Our study identified the biological role of the circROBO1-miR-556-5p-PGK1 axis in the growth and enzalutamide resistance of prostate cancer, which is the potential therapeutic target of prostate cancer.

Isoliquiritigenin inhibits circ0030018 to suppress glioma tumorigenesis via the miR-1236/HER2 signaling pathway.

In the central nervous system diseases, glioma is one of the most common malignancies around the world. Despite the recent improvements in therapies for glioma, the prognosis of some high-risk glioma remains poor. In glioma, isoliquiritigenin (ISL) is reported to have antioxidative and antitumor activities. However, the potential mechanisms between ISL and circle RNAs (circRNAs) in the glioma tumorigenesis process have not yet been reported. Here, we treated glioma cells with ISL, and circRNA expression levels were detected. Circ0030018 was found significantly downregulated by ISL. Therefore, we explored circ0030018 expression profiles and functions in glioma, finding that circ0030018 was evidently overexpressed in glioma cell lines. Colony formation, CCK-8, and transwell assay made clear that circ0030018 silencing dramatically cut down glioma growth and invasion. Moreover, ROS level was detected to find that circ0030018 silence remarkably enhanced cell oxidative stress in glioma. Mechanism studies were conducted to investigate the underlying basis of circ0030018 function in glioma, unveiling that circ0030018 realized its functions partially through the miR-1236/HER2 signaling in glioma. In conclusion, our study investigated the roles and mechanisms of the ISL on the circ0030018/miR-1236/HER2 pathway in glioma tumorigenesis and progression. Circ0030018 could act as the prospective biologic signature or therapeutic target for glioma.

The Single-Cell Landscape of Intratumoral Heterogeneity and The Immunosuppressive Microenvironment in Liver and Brain Metastases of Breast Cancer.

Distant metastasis remains the major cause of morbidity for breast cancer. Individuals with liver or brain metastasis have an extremely poor prognosis and low response rates to anti-PD-1/L1 immune checkpoint therapy compared to those with metastasis at other sites. Therefore, it is urgent to investigate the underlying mechanism of anti-PD-1/L1 resistance and develop more effective immunotherapy strategies for these patients. Using single-cell RNA sequencing, a high-resolution map of the entire tumor ecosystem based on 44 473 cells from breast cancer liver and brain metastases is depicted. Identified by canonical markers and confirmed by multiplex immunofluorescent staining, the metastatic ecosystem features remarkable reprogramming of immunosuppressive cells such as FOXP3+ regulatory T cells, LAMP3+ tolerogenic dendritic cells, CCL18+ M2-like macrophages, RGS5+ cancer-associated fibroblasts, and LGALS1+ microglial cells. In addition, PD-1 and PD-L1/2 are barely expressed in CD8+ T cells and cancer/immune/stromal cells, respectively. Interactions of the immune checkpoint molecules LAG3-LGALS3 and TIGIT-NECTIN2 between CD8+ T cells and cancer/immune/stromal cells are found to play dominant roles in the immune escape. In summary, this study dissects the intratumoral heterogeneity and immunosuppressive microenvironment in liver and brain metastases of breast cancer for the first time, providing insights into the most appropriate immunotherapy strategies for these patients.

Circular RNAs in breast cancer diagnosis, treatment and prognosis.

Breast cancer has surpassed lung cancer to become the most common malignancy worldwide. The incidence rate and mortality rate of breast cancer continue to rise, which leads to a great burden on public health. Circular RNAs (circRNAs), a new class of noncoding RNAs (ncRNAs), have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression. In breast cancer, circRNAs have significant roles in tumorigenesis, recurrence and multidrug resistance that are mediated by various mechanisms. Therefore, circRNAs may serve as promising targets of therapeutic strategies for breast cancer management. This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis, treatment and prognosis evaluation, as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer. Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.

tRNA-derived fragments in gastric cancer: Biomarkers and functions.

tRNA-derived fragments (tRFs), non-coding RNAs that regulate protein expression after transcription, have recently been identified as potential biomarkers. We identified differentially expressed tRFs in gastric cancer (GC) and the biological properties of tRFs in predicting the malignancy status of GCs as possible biomarkers. Until 15 February 2022, two independent reviewers did a thorough search in electronic databases of Scopus, EMBASE and PubMed. The QUADAS scale was used for quality assessment of the included studies. Ten articles investigating the clinical significance of tRFs, including 928 patients, were analysed. In 10 GC studies, seven tRFs were considerably upregulated and five tRFs were significantly downregulated when compared to controls. Risk of bias was rated low for index test, and flow as well as timing domains in relation to the review question. The applicability of the index test, flow and timing and patient selection for 10 studies was deemed low. In this study, we review the advances in the study of tRFs in GC and describe their functions in gene expression regulation, such as suppression of translation, cell differentiation, proliferation and the related signal transduction pathways associated with them. Our findings may offer researchers new ideas for cancer treatment as well as potential biomarkers for further research in GC.

Corrigendum: AFAP1-AS1 Promotes Epithelial-Mesenchymal Transition and Tumorigenesis Through Wnt/ß-Catenin Signaling Pathway in Triple-Negative Breast Cancer.

[This corrects the article DOI: 10.3389/fphar.2018.01248.].

miR-200c suppresses stemness and increases cellular sensitivity to trastuzumab in HER2+ breast cancer.

Resistance to trastuzumab remains a major obstacle in HER2-overexpressing breast cancer treatment. miR-200c is important for many functions in cancer stem cells (CSCs), including tumour recurrence, metastasis and resistance. We hypothesized that miR-200c contributes to trastuzumab resistance and stemness maintenance in HER2-overexpressing breast cancer. In this study, we used HER2-positive SKBR3, HER2-negative MCF-7, and their CD44+ CD24- phenotype mammospheres SKBR3-S and MCF-7-S to verify. Our results demonstrated that miR-200c was weakly expressed in breast cancer cell lines and cell line stem cells. Overexpression of miR-200c resulted in a significant reduction in the number of tumour spheres formed and the population of CD44+ CD24- phenotype mammospheres in SKBR3-S. Combining miR-200c with trastuzumab can significantly reduce proliferation and increase apoptosis of SKBR3 and SKBR3-S. Overexpression of miR-200c also eliminated its downstream target genes. These genes were highly expressed and positively related in breast cancer patients. Overexpression of miR-200c also improved the malignant progression of SKBR3-S and SKBR3 in vivo. miR-200c plays an important role in the maintenance of the CSC-like phenotype and increases drug sensitivity to trastuzumab in HER2+ cells and stem cells.

Is surgical axillary staging necessary in women with T1 breast cancer who are treated with breast-conserving therapy?

BACKGROUND: In the post-Z0011 trial era, the need to perform surgical axillary staging for early-stage breast cancer patients, who are treated with breast-conserving therapy (BCT), is being questioned. We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the safety of waiving surgical axillary staging in patients with T1 breast cancer treated with BCT. METHODS: A total of 166,615 eligible patients diagnosed between 2000 and 2012 were divided into staging (sentinel lymph node biopsy or axillary lymph node dissection) and non-staging (no lymph node examined or only needle aspiration biopsy of lymph nodes) groups. Propensity score matching (PSM) was performed to balance disparities between the two groups. Multivariate analysis with the Cox proportional hazards model was used to assess factors related to breast cancer-specific survival (BCSS). RESULTS: Although the tumor size at time of presentation was decreasing over years, the rate of surgical axillary staging increased from 93.3% to 96.9%. The 5-year BCSS rates of the whole cohort (before PSM) and matched cohort (after PSM) were 98.0% and 97.5%. Within the matched cohort, the BCSS was significantly longer in the staging group than in the non-staging group (P < 0.001). However, surgical axillary staging did not benefit patients who were 50-79 years old, had tumor size < 1 cm, histological grade I disease, or favorable histological types (tubular/mucinous/papillary) in stratified analyses (P > 0.05). Race, marital status, hormone receptors, and chemotherapy were not associated with the favorable impact of surgical axillary staging on BCSS (P > 0.05). CONCLUSION: Although surgical axillary staging remains important for T1 breast cancer patients treated with BCT, it might be unnecessary for patients with old age, small tumor, grade I disease, or favorable histological types.

AFAP1-AS1 Promotes Epithelial-Mesenchymal Transition and Tumorigenesis Through Wnt/ß-Catenin Signaling Pathway in Triple-Negative Breast Cancer.

Long non-coding RNA (LncRNA) actin filament-associated protein1-antisense RNA 1 (AFAP1-AS1) is overexpressed in various types of cancers and plays an important role in tumor progression and prognosis. This study investigates the role of AFAP1-AS1 in tumor progression in triple-negative breast cancer (TNBC). We found that AFAP1-AS1 was overexpressed in TNBC tissues and cells. Overexpression of LncRNA AFAP1-AS1 was associated with poor prognosis in TNBC patients. Moreover, we demonstrated that upregulation of AFAP1-AS1 promoted cell proliferation and invasion, and inhibited cell apoptosis in vitro, while overexpression of AFAP1-AS1 promoted tumor growth in vivo. Our results also revealed that upregulation of AFAP1-AS1 activated Wnt/ß-catenin pathway to promote tumorigenesis and cell invasion by increasing the expression of C-myc and epithelial-mesenchymal transition-related molecules in TNBC. Collectively, AFAP1-AS1 can be an independent prognostic marker and an effective therapeutic target of triple- negative breast cancer.

SOX2 Promotes Cell Proliferation and Metastasis in Triple Negative Breast Cancer.

This study explored the expression, biological function and prognostic role of SOX2 in triple negative breast cancer (TNBC). Quantitative real-time PCR and immunohistochemistry were used to detect the expression of SOX2 in TNBC cell lines and clinical tissues. MTT assay, Transwell assay, flow cytometry and xenograft mouse model were used to assess the biological functions of SOX2. It was found that SOX2 was up-regulated in both TNBC cell lines and clinical tissues. High expression of SOX2 was associated with shorter overall survival and disease free survival. Moreover, inhibition of SOX2 suppressed cell proliferation and invasion, induced cell apoptosis in vitro, and suppressed tumorigenesis and metastasis in vivo. In addition, analysis of TNM stage and lymph nodes infiltration among the 237 TNBC patients by paired χ2 test showed that SOX2 was inversely correlated with tumor status, our findings provided evidence that SOX2 acts as a tumor promoter in TNBC and inhibition of SOX2 could be a potential therapeutic strategy for TNBC.

Adam12 and lnc015192 act as ceRNAs in breast cancer by regulating miR-34a.

Long non-coding RNAs (lncRNAs) are reported to play vital roles in the progress of multiple cancers. However, the functions of lncRNAs in breast cancer remain to be discovered. We performed microarrays to identify the differentially expressed mRNAs and lncRNAs in breast tissues with or without miR-34a knockout. To explore the functions of the differentially expressed mRNA and lncRNA in breast cancer, we conducted a series of experiments. We found that Adam12 and lnc015192 were significantly upregulated in miR-34a knockout breast tissues. Knockdown of Adam12 and lnc015192 inhibited breast cancer cell migration, invasion, and epithelial-mesenchymal transition (EMT). Further experiments revealed that lnc015192 regulated Adam12 expression by functioning as a competing endogenous RNA (ceRNA) for miR-34a. In summary, our study demonstrate that Adam12 and lnc015192 promote breast cancer metastasis partly by sponging miR-34a through the ceRNA mechanism.

FOXP2 Promotes Tumor Proliferation and Metastasis by Targeting GRP78 in Triple-negative Breast Cancer.

BACKGROUND: FOXP2, a member of the forkhead box P (FOXP) family, has been reported to be important in breast cancer. However, its exact mechanisms and pathways remain unclear. OBJECTIVE: To investigate the effect of FOXP2 on tumor proliferation and metastasis in triplenegative breast cancer (TNBC) and study its underlying molecular mechanism. METHODS: We first used qRT-PCR to detect FOXP2 expression in TNBC cell lines and tissues. Then we conducted cell proliferation assays, colony formation assays, and transwell assays to analyze the effects of FOXP2 expression in TNBC cells. Mouse xenograft model was performed to further confirm the role of FOXP2 in TNBC. Moreover, we used qRT-PCR and Western blot to access the effect of FOXP2 on GRP78 expression and qRT-PCR to analyze GRP78 expression in TNBC tissues. We conducted IHC analysis to detect both FOXP2 and GRP78 expressions in transplanted tumors and used the correlation analysis to further analyze the link between them. RESULTS: FOXP2 was found to be highly expressed in TNBC cell lines and tissues. FOXP2 knockdown attenuated the growth and invasiveness of TNBC in vitro as well as tumor progression and metastasis in vivo. Moreover, FOXP2 knockdown downregulated glucose-regulated protein of molecular mass 78 (GRP78) expression in TNBC cells and transplanted tumors. Correlation analysis showed that GRP78 expression was positively associated with FOXP2 expression in TNBC cells. CONCLUSION: FOXP2 plays a crucial role in TNBC, partly through modulating GRP78, and could act as a potential target for TNBC treatment.