Hsa_circRNA_0000518 facilitates breast cancer development via regulation of the miR-326/FGFR1 axis.

BACKGROUND: Breast cancer (BC) is a heterogeneous malignant tumor that threatens the health of women worldwide. Hsa_circRNA_0000518 (circ_0000518) has been revealed to be upregulated in BC tissues. However, the role and mechanism of circ_0000518 in BC are indistinct. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was implemented to detect the levels of circ_0000518, microRNA (miR)-326, and fibroblast growth factor receptor 1 (FGFR1) mRNA in BC tissues and cells. Cell counting kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays were executed to estimate BC cell proliferation, cell cycle progression, apoptosis, migration, and invasion. The relationship between circ_0000518 or FGFR1 and miR-326 was verified by dual-luciferase reporter and/or RNA immunoprecipitation (RIP) assays. The role of circ_0000518 in vivo was confirmed by xenograft assay. RESULTS: Circ_0000518 and FGFR1 were upregulated while miR-326 was downregulated in BC tissues and cells. Circ_0000518 silencing impeded tumor growth in vivo and induced cell cycle arrest, apoptosis, cured proliferation, colony formation, migration, and invasion of BC cells in vitro. Circ_0000518 regulated FGFR1 expression via competitively binding to miR-326 in BC cells. MiR-326 inhibitor reversed the inhibitory influence of circ_0000518 knockdown on the malignant behaviors of BC cells. FGFR1 overexpression abolished miR-326 mimic-mediated influence on the malignant behaviors of BC cells. CONCLUSIONS: Circ_0000518 facilitated BC development via regulation of the miR-326/FGFR1 axis, suggesting that circ_0000518 might be a promising target for BC treatment.

Upregulated expression of AT-rich interactive domain-containing protein 1B predicts poor prognosis in patients with triple-negative breast cancer.

The expression of AT-rich interactive domain-containing protein 1B (ARID1B) was investigated in triple-negative breast cancer (TNBC). The association between ARID1B protein expression and the prognosis of patients with TNBC was investigated. The expression of ARID1B was examined in TNBC (n=142) and adjacent normal breast tissues (n=64) using immunohistochemical staining prior to the patients receiving any treatment. Furthermore, the association between ARID1B protein expression and various clinicopathological features was analyzed, including the survival status of patients with TNBC. Of the 142 TNBC tissues, ARID1B was highly expressed in 89 (62.7%) and poorly expressed in 53 (37.3%). ARID1B expression was associated with lymph node metastasis status, histological grade and p53 expression. ARID1B expression was upregulated significantly in the nuclei of TNBC cells compared with those of normal mammary epithelial cells. This upregulation was associated with a decreased progression-free survival rate (P=0.002) and overall survival rate (P=0.003). The results of the present study indicate that significant association exists between the nuclear expression of ARID1B and adverse prognosis in TNBC. Therefore, ARID1B may be a useful prognostic biomarker in TNBC.

The associations of genetic polymorphisms in CYP1A2 and CYP3A4 with clinical outcomes of breast cancer patients in northern China.

BACKGROUND: Cytochrome P450 (CYP) 1A2 and CYP3A4 may play a role in the differentiation of clinical outcomes among breast cancer women. This study aimed to analyze the association of genetic polymorphisms in the CYP1A2 and CYP3A4 genes with clinicopathological features, protein expression and prognosis of breast cancer in the northern Chinese population. RESULTS: Firstly, SNP rs11636419, rs17861162 and rs2470890 in the CYP1A2 were significantly associated with age and menstruation status. And SNP rs11636419 and rs17861162 were associated with the P53 status. Secondly, SNP rs2470890 was correlated with CYP1A2 protein expression under the co-dominant and dominant model (P = 0.017, P = 0.006, respectively). Thirdly, for SNP rs2470890, the Kaplan-Meier 5 year survival curves showed that patients carrying genotypes CT or TT had a worse OS compared with the genotype CC carriers under both codominant and dominant model (P < 0.001, P < 0.001, respectively). MATERIALS AND METHODS: Four single nucleotide polymorphisms (SNPs) were successfully genotyped in 459 breast cancer patients using the SNaPshot method. The associations of four polymorphisms with protein expression and clinicopathological characteristics were evaluated by Pearson's chi-square test. The Cox hazard regression analysis and Kaplan-Meier survival analysis were performed to evaluate the relationship between the SNPs and overall survival (OS) of breast cancer. CONCLUSIONS: CYP1A2 rs2470890 was significantly associated with the prognosis of patients with breast cancer and could serve as an independent impact factor of prognosis of breast carcinoma.

A High-Quality Biobank Supports Breast Cancer Research in Harbin, China.

We established a standard breast cancer biobank at Harbin Medical University Cancer Hospital (HMUCH) in 2009. More than 100,000 biospecimens, including high-quality human breast cancer samples, matched blood samples, and adjacent normal tissues, were collected from patients and healthy donors in HMUCH and were then deposited in the repository. We reported the establishment of a biobank in our hospital and its crucial role in translational medicine research. We stored, processed, and distributed qualified biological specimens in accordance with international standard operating procedures. We also summarized the utilization of this biobank and its influence on research projects over the years since its establishment. Therefore, we can verify specific biomarkers that may aid in the development of targeted breast cancer therapies by using high-quality, well-annotated tissue samples provided by the biobank.

The long non-coding RNA EPB41L4A-AS2 inhibits tumor proliferation and is associated with favorable prognoses in breast cancer and other solid tumors.

EPB41L4A-AS2 is a novel long non-coding RNA of unknown function. In this study, we investigated the expression of EPB41L4A-AS2 in breast cancer tissues and evaluated its relationship with the clinicopathological features and prognosis of patients with breast cancer. This entailed conducting a meta-analysis and prognosis validation study using two cohorts from the Gene Expression Omnibus (GEO). In addition, we assessed EPB41L4A-AS2 expression and its relationship with the clinicopathological features of renal and lung cancers using the Cancer Genome Atlas cohort and a GEO dataset. We also clarified the role of EPB41L4A-AS2 expression in mediating cancer cell proliferation in breast, renal, and lung cancer cell lines transfected with an EPB41L4A-AS2 expression vector. We found that high EPB41L4A-AS2 expression is associated with favorable disease outcomes. Gene ontology enrichment analysis revealed that EPB41L4A-AS2 may be involved in processes associated with tumor biology. Finally, overexpression of EPB41L4A-AS2 inhibited tumor cell proliferation in breast, renal, and lung cancer cell lines. Our clinical and in vitro results suggest that EPB41L4A-AS2 inhibits solid tumor formation and that evaluation of this long non-coding RNA may have prognostic value in the clinical management of such malignancies.

Study of circulating antibodies against CD25 and FOXP3 in breast cancer.

Our recent work suggests that circulating levels of anti-CD25 and anti-FOXP3 antibodies were significantly increased in patients with either lung cancer or esophageal cancer. To confirm if these two autoantibodies are specific for certain types of malignant tumors, the present work was thus undertaken to examine an alteration of anti-CD25 and anti-FOXP3 IgG levels in breast cancer. A total of 152 patients with breast cancer and 112 control subjects were recruited in this study. The levels of circulating anti-CD25 and anti-FOXP3 IgG antibodies were tested using an in-house enzyme-linked immunosorbent assay (ELISA). Student's t test showed no significant differences in the levels of either anti-CD25 IgG or anti-FOXP3 IgG between patients with breast cancer and control subjects, although patients at stage I had increased levels of anti-CD25 IgG compared with control subjects (t = 2.11, P = 0.037); there was no significant association of the anti-FOXP3 IgG levels with stages of breast cancer. In conclusion, circulating IgG autoantibody to CD25 instead of FOXP3 may be a potential biomarker for early diagnosis of breast cancer but further investigation remains needed to replicate this initial finding.