Xi Gu

MicroRNA-148a inhibits migration of breast cancer cells by targeting MMP-13.

Breast cancer is a threat to the health of women, and metastasis of breast cancer cells plays an important role in the deterioration of breast cancer. MicroRNAs play a critical role in the tumorigenesis and development of breast cancer. MicroRNA-148a (miR-148a) is associated with the growth and metastasis of tumor cells. In the present study, we investigated the role of miR-148a in migration of breast cancer cells as well as the underlying mechanism. MiR-148a was found to inhibit the proliferation and migration of breast cancer cells. To further explore the mechanism through which miR-148a plays its antitumor role, matrix metalloproteinase-13 (MMP-13) was identified as a target of miR-148a by western blot and luciferase reporter assay. Moreover, silence of MMP-13 mimicked the effect of miR-148a, whereas overexpression of MMP-13 rescued the impaired migration caused by miR-148a. Our study demonstrates that miR-148a inhibits the migration of breast cancer cells by targeting MMP-13 and also lays theoretical foundation for further exploration for the function of miR-148a.

Circulating microRNA-451 as a predictor of resistance to neoadjuvant chemotherapy in breast cancer

OBJECTIVE We aimed to explore the potential application of circulating microRNA-451 (miR-451) in serum in predicting the resistance to neoadjuvant chemotherapy (NACT) in breast cancer (BC). METHODS Eighty-two BC patients who underwent NACT were recruited in our study, including 41 NACT-sensitive patients (NACT-sensitive group) and 41 NACT-resistant patients (NACT-resistant group). Additionally, 60 healthy subjects were selected as normal controls. Epirubicin-resistant MCF-7 BC cell line (MCF-7/EPI) and docetaxel-resistant MCF-7 BC cell line (MCF-7/DOC) were cultured in our study. MTT assay was applied to calculate the survival rates of MCF-7 cells, MCF-7/DOC cells and MCF-7/EPI cells. The expression levels of miR-451 in normal controls, NACT-sensitive group, NACT-resistant group, MCF-7 cells, MCF-7/DOC cells and MCF-7/EPI cells were measured by qRT-PCR method. RESULTS The proliferation rates of both the MCF-7/DOC and MCF-7/EPI cells were significantly restrained at the drug concentration of 10 ng/ml, 50 ng/ml, 100 ng/ml and 200 ng/ml. However, the proliferation rates of MCF-7/DOC and MCF-7/EPI cells both increased significantly at the drug concentration of 500ng/ml. Furthermore, the IC50 of MCF-7/DOC cells was 23.603 ng/ml and the IC50 of MCF-7/EPI cells was 3.209 ng/ml. The relative expression of miR-451 was significantly lower in both the NACT-resistant group and the NACT-sensitive group than the normal control group. We also found that the relative expression level of miR-451 was significantly lower in the NACT-resistant group than that in the NACT-sensitive group. The expression of miR-451 in the MCF-7/EPI and the MCF-7/DOC cell lines was significantly lower than that in the MCF-7 cell lines. CONCLUSION We supported the view that the relative expression level of miR-451 was lower in the NACT-resistant BC patients, suggesting the circulating miR-451 may have a functional significance in predicting the resistance to NACT in BC patients. We laid a foundation for further research on the resistance to NACT in BC treatment.

Influence of MiR-451 on Drug Resistances of Paclitaxel-Resistant Breast Cancer Cell Line

Background This study aimed to investigate the potential influence of microRNA-451 (miR-451) in drug resistances of the Paclitaxel-resistant breast cancer cell line by transfecting miR-451 mimics and miR-451 inhibitors to MCE-7, MCF-7/EPI, and MCF-7/DOC. Material/Methods Real-time quantitative PCR (qRT-PCR) was performed for detecting whether transfected miR-451 mimics and miR-451 inhibitors could regulate the expression of miR-451 effectively. The apoptosis of the 3 cell lines was measured by applying Annexin V-APC/PI staining. Western blot was used for the detection of the protein expression of Bcl-2 and Caspase 3 after the transfection of miR-451 mimics /inhibitors. Bioinformatics analysis demonstrated that Bcl-2 protein is a potential target gene for miR-451. Results In comparison to the control group, after transfection with miR-451 mimics, there was a significant increase in miR-451 expression in MCF-7, MCF-7/EPI, and MCF-7/DOC. Cells in the three cell lines had increased apoptosis, Bcl-2 protein expression decreased significantly, and Caspase protein expression increased obviously. After the transfection with miR-451 inhibitors, miR-451 expression was significantly decreased and apoptosis in the 3 cell lines had no significant decrease compared with the control group. Conclusions Increased miR-451 expression may negatively regulate Bcl-2 mRNA and protein expression, followed by affecting the protein expression of caspase 3, and accelerate the apoptosis in breast cancer, indicating that miR-451 might influence the drug resistances of the Paclitaxel-resistant breast cancer cell line.

Intercostobrachial nerves as a novel anatomic landmark for dividing the axillary space in lymph node dissection.

Purpose. Our aim was to assess the feasibility of using the intercostobrachial nerves (ICBNs) as a possible new anatomic landmark for axillaries lymph node dissection in breast cancer patients. Background Data Summary. The preservation of ICBN is now an accepted procedure in this type of dissection; however, it could be improved further to reduce the number of postoperative complications. The axillary space is divided into lower and upper parts by the ICBN—a thorough investigation of the metastasis patterns in lymph nodes found in this area could supply new information leading to such improvements. Methods. Seventy-two breast cancer patients, all about to undergo lymph node dissection and with sentinel lymph nodes identified, were included in this trial. The lymph nodes were collected in two groups, from lower and upper axillary spaces, relative to the intercostobrachial nerves. The first group was further subdivided into sentinel (SLN) and nonsentinel (non-SLN) nodes. All lymph nodes were tested to detect macro- and micrometastasis. Results. All the sentinel lymph nodes were found under the intercostobrachial nerves; more than 10 lymph nodes were located in that space. Moreover, when lymph nodes macrometastasize or micrometastasize above the intercostobrachial nerves, we also observe metastasis-positive nodes under the nerves; when the lower group nodes show no metastasis, the upper group is also metastasis free. Conclusions. Our results show that the intercostobrachial nerves are good candidates for a new anatomic landmark to be used in lymph node dissection procedure.

A New Technique That Complements Sentinel Lymph Node Biopsy: Lymph Node Dissection Under the Intercostobrachial Nerves in Early-Stage Breast Cancer

BACKGROUND Arm lymphedema is a common complication after axillary lymph node dissection (ALND), and there is no effective treatment. The clinical significance of sentinel lymph node biopsy (SLNB) is to avoid the risk of arm lymphedema caused by ALND in cases in which the nodes are negative for cancer cells. In developed countries, sentinel lymph node (SLN) localization methods by using combined dye and radioactive tracer techniques predict the lymph node status in early-stage breast cancer with comparable success rates, accuracy, and false-negative rates. In fact, most researchers agree that the combined technique has significantly higher accuracy than marking the sentinel nodes with dye alone. In China, the radioactive tracer technique is mostly used in research but not in clinical surgery, where it is not permitted. The necessity of intercostobrachial nerves (ICBN) preservation is now accepted by the surgeons and has become the standard procedure in such dissections, which reduces postoperative skin numbness and loss of feeling in the upper arm. METHODS In our study, the data of 177 patients were analyzed to identify the feasibility of such an assignment and potential clinical significance of ICBN in dividing the axillary space. RESULTS We found that the mean value for the number of nodes under the ICBN was enough for accession, the lymphedema caused by axillary lymph nodes dissection under the intercostobrachial nerves (PALND) was similar with SLNB and lower than ALND, and the PALND can make up for SLNB in false negative (SLNs are negative, while non-SLNs are positive). CONCLUSION ALND under the ICBN could be considered a procedure complementary to SLNB in early-stage breast cancer in China, where the radioactive tracer technique is not widely applied.

Retraction Note to: Aberrant promoter methylation of the CHD1 gene may contribute to the pathogenesis of breast cancer: a meta-analysis

Cadherin-1 (CHD1), as an invasion suppressor gene, could suppress tumor cell invasion and metastasis in various tumors, but reduced CHD1 levels, resulting from epigenetic silencing, are common in poorly differentiated, advanced stage carcinomas. This meta-analysis was performed to evaluate the relationships between promoter methylation of CHD1 and breast cancer. Relevant studies were retrieved from the Web of Science (1945 ~ 2013), the Cochrane Library (Issue 12, 2013), PubMed (1966 ~ 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013) using a systematic literature search. Results were summarized by meta-analyses, conducted using the STATA software (version 12.0, Stata Corporation, College Station, TX, USA). Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were calculated. In the present meta-analysis, 9 cohort studies with a total of 425 patients with breast cancer were included. Our meta-analysis results demonstrated that the frequency of CHD1 promoter methylation in cancer tissues was significantly higher than that in normal tissues, adjacent tissues, and benign tissues (cancer tissue vs. normal tissue OR = 30.87, 95 % CI = 16.76 ~ 56.86, P < 0.001; cancer tissue vs. adjacent tissue OR = 23.30, 95 % CI = 12.85 ~ 42.26, P < 0.001; cancer tissue vs. benign tissue OR = 2.94, 95 % CI = 1.60 ~ 5.40, P < 0.001; respectively). Ethnicity-stratified analysis indicated that aberrant CHD1 promoter methylation was strongly correlated with breast cancer among both Asians and Caucasians in the majority of subgroups. Our results suggest that aberrant promoter methylation of the CHD1 gene may have a high frequency in breast cancer tissues. Thus, CHD1 methylation could be correlated with the pathogenesis of breast cancer.