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@#Objective: To investigate the expressions of miR-144 and lncRNA DNAJC3-AS1 in breast cancer tissues and their effects on chemo-resistance of breast cancer MCF-7 cells. Methods: A total of 196 pairs of breast cancer tissues and corresponding adjacent normal tissues collected between January, 2012 and December, 2016 in Department of Oncology, 3201 Hospital were used for this study. The relative expressions of DNAJC3-AS1, DNAJC3 and miR-144 in collected tissues were determined using qPCR, and their impact on the survival of BC patients was also analyzed. The targeted binding relationship between DNAJC3-AS1 and miR-144 was verified by Luciferase reporter gene assay. DNAJC3-AS1 over-expression plasmid and miR-144 mimics were transfected into MCF-7 cell lines respectively, and qPCR was used to verify the transfection efficiency. The effects of DNAJC3-AS1 and miR-144 overexpression on proliferation and cisplatin sensitivity of MCF-7 cells were verified by CCK-8 assay. Results: DNAJC3-AS1 and its host gene DNAJC3 were highly expressed in BC tissues (all P<0.01), and these two were positively correlated (r=0.451, P<0.01); in addition, patients with high expressions of DNAJC3-AS1 and DNAJC3 had a shorter survival period (all P<0.01). miR-144 was highly expressed in BC tissues (P<0.01) and negatively correlated with DNAJC3-AS1 (r=-0.524, P<0.01). The average over-expressionfold for DNAJC3-AS1 was 13.47 (P<0.01), while the fold for miR-144 was 20.27 (P<0.01). Bioinformatics analysis and fluorescence reporter gene assay confirmed that DNAJC3-AS1 could specifically bind to miR-144. MCF-7 cell lines over-expressing DNAJC3-AS1 and miR-14 were successfully constructed; compared with control group, cells in DNAJC3-AS1 over-expression group exhibited significantly enhanced proliferation and reduced cisplatin-sensitivity (all P<0.01), while the cells in miR-144 over-expression group showed significantly enhanced drug sensitivity (P<0.01). Conclusion: miR-144 and lncDNAJC3-AS1 were highly expressed in BC tissues, miR-144 promotes cisplatin sensitivity of BC MCF-7 cells through targeting DNAJC3-AS1.
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The aim of this study was to identify some biomarkers for predicting lymph node metastasis and prognosis of human epidermal growth factor receptor 2 (Her-2)-positive breast cancer (BC). We analyzed correlations between microRNAs (miRNAs) and the prognosis of patients with BC based on data collected from The Cancer Genome Atlas (TCGA) database. The expression levels of miR-455, miR-143, and miR-99a were measured in clinical samples of Her-2-positive BC patients with different degrees of lymph node metastasis. We investigated the impacts of overexpressed miR-455 on the proliferation and invasiveness of MDA-MB-453 cells and measured its effects on the expression of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of miR-455 was significantly and positively correlated to the prognosis and overall survival (OS) of the BC (P=0.028), according to TCGA information. The expression level of miR-455 was positively correlated with OS and relapse-free survival (RFS) of patients with Her-2-positive BC, and was negatively correlated with the number of metastatic lymph nodes (P<0.05). Transwell assay suggested that MDA-MB-453 cells became much less invasive (P<0.01) after being transfected with miR-455 mimics. During the qRT-PCR, the expression level of MALAT1 declined significantly after transfection (P<0.01). Overexpressed miR-455 significantly inhibited the proliferation and migration of MDA-MB-453 cells and the expression of MALAT1. We conclude that miR-455 may be a useful potential biomarker for forecasting lymph node metastasis and the prognosis of Her-2-positive BC patients. miR-455 may play an important role in lymph node metastasis of BC by interacting with MALAT1.
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@#Objective: To detect the expression of GRHL2 (grainyhead-like-2) in breast cancer tissues and to explore its correlation with clinicopathological characteristics and prognosis of breast cancer (BC) patients，aiming to find new therapeutic target for breast cancer. Method: A total of 88 pairs of BC tissues and corresponding para-cancerous tissues from patients with primary BC that treated and pathologically confirmed at the Second Department of General Surgery, Xinxiang Central Hospital from January 2010 to January 2017 were collected for this study. The expression of GRHL2 in BC tissues and para-cancerous tissues was examined with IHC, and the association between GRHL2 and clinicopathological characteristics of BC patients was analyzed. Moreover, the correlation between GRHL2 and prognosis of BC patients was investigated by analyzing TCGA clinic data for BC. Result: The expression of GRHL2 was significantly higher in BC tissues (75.00%) compared with para-cancerous tissues (36.36%) (P<0.01); Based on the results of GRHL2 expression in 114 cases of normal breast tissues and 1 097 cases of primary breast cancer tissues in TCGA database, the expression of GRHL2 in primary BC tissues was significantly higher than that in normal breast tissues (P<0.01). GRHL2 expression was associated with BC TNM stage,histological grade, HER2 status and lymphnode metastasis status (all P<0.05); TCGA database showed that the RFS of 1 979 BC patients with high GRHL2 expression was significantly shorter than that of the 1 972 cases of BC patients with low GRHL2 expression (HR=1.24, 95%CI:1.11-1.38, P<0.01); GRHL2 expression exerted no significant effect on RFS of TNBC patients or ER+ BC patients (TNBC: HR=1.30，95%CI: 0.89-1.88，P=0.170; ER+: HR=1.17, 95%CI:0.76-1.78， P=0.470); however, the RFS of HER2+ BC patients with high GRHL2 expression was significantly shorter than that of HER2+ BC patients with low GRHL2 expression (HR=1.72, 95%CI:1.11-2.68, P=0.015） . Conclusion：Expression level of GRHL2 was up-regulated in BC tissues, and was associated with BC TNM stage, histological grade, HER2 status and the lymphnode metastasis status. GRHL2 plays an important role in the generation and development of BC, indicating poor prognosis.
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Objective To investigate the clinical significance of serum vitamin D levels change in patients with breast cancer (BC) before and after radiotherapy and chemotherapy.Methods A total of 100 BC patients and 100 healthy controls were enrolled in the First Affiliated Hospital of Xi'an Jiaotong University from June 2016 to June 2017. All the patients received adjuvant chemotherapy and radiotherapy after operation. Serum 25-hydroxyvitamin D3 (25-OHD) levels were measured using the DRG ELISA kit.Results There was no significant difference in age, BMI, times of deliveries, hemoglobin level, total lymphocyte count and platelet count between the cases and the controls (P＞0.05). The incidence of vitamin deficiency was 100％ in the case group and 85％ in the control group. The level of serum vitamin D was (16.63 ± 1.83) ng/ml in the case group before radiotherapy and chemotherapy, and (25.56 ± 6.64) ng/m L in the control group. The level of vitamin D before radiotherapy and chemotherapy in the case group was significantly lower than that of the control group (P＜ 0.001). The mean level of vitamin D was (11.35 ± 2.87) ng/m L after radiotherapy and was significantly lower than that before radiotherapy and chemotherapy (P＜0.001). Two different chemotherapy regimens were used in this study, FEC/T and CMF regimens. Before radiotherapy and chemotherapy, there was no significant difference in vitamin D levels between the two groups (P＞0.05). After radiotherapy and chemotherapy, vitamin D levels in both groups were significantly decreased (P＜0.001), but there was no significant difference between the two groups in vitamin D levels (P＞0.05). Multiple regression analysis showed that age, BMI and number of deliveries were significantly correlated with changes of vitamin D levels before and after radiotherapy and chemotherapy (P＜0.05), and correlations were as follows: age, BMI and times of deliveries.Conclusion Vitamin D deficiency may be associated with breast cancer. Patients' age, BMI and times of deliveries were significantly correlated with vitamin D levels before and after radiotherapy and chemotherapy.