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Tamoxifen is commonly used for the treatment of patients with estrogen receptor‐positive (ER+) breast cancer, but the acquired resistance to tamoxifen presents a critical challenge of breast cancer therapeutics. Recently, long noncoding RNA MIR497HG and its embedded miR‐497 and miR‐195 are proved to play significant roles in many types of human cancers, but their roles in tamoxifen‐resistant breast cancer remain unknown. The results indicate that MIR497HG deficiency induces breast cancer progression and tamoxifen resistance by inducing downregulation of miR‐497/195. miR‐497/195 coordinately represses five positive PI3K‐AKT regulators (MAP2K1, AKT3, BCL2, RAF1, and CCND1), resulting in inhibition of PI3K‐AKT signaling, and PI3K‐AKT inhibition in tamoxifen‐resistant cells restored tamoxifen responsiveness. Furthermore, ER α binds the MIR497HG promoter to activate its transcription in an estrogen‐dependent manner. ZEB1 interacts with HDAC1/2 and DNMT3B at the MIR497HG promoter, resulting in promoter hypermethylation and histone deacetylation. The findings reveal that ZEB1‐induced MIR497HG depletion contributes to breast cancer progression and tamoxifen resistance through PI3K‐AKT signaling. MIR497HG can be used as a biomarker for predicting tamoxifen sensitivity in patients with ER+ breast cancer. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) remains the leading cause of cancer‐related deaths worldwide. High recurrence risk Luminal BC receives adjuvant chemotherapy in addition to standard hormone therapy. Considering the heterogeneity of Luminal B BC, a more accurate classification model is urgently needed. Methods: In this study, we retrospectively reviewed the data of 1603 patients who were diagnosed with HER2‐negative breast invasive ductal carcinoma. According to the expression level of PR and Ki‐67 index, the Luminal B (HER2‐negative) BCs were divided into three groups: ER+PR−Ki67low (ER‐positive, PR‐negative, and Ki‐67 index <20%), ER+PR+Ki67high (ER‐positive, PR‐positive, and Ki‐67 index ≥20%), and ER+PR−Ki67high (ER‐positive, PR‐negative, and Ki‐67 index ≥20%). The cox proportional hazards regression model was used to evaluate the correlation between each variable and outcomes. Besides, discriminatory accuracy of the models was compared using the area under the receiver operating characteristic curve and log‐rank χ2 value. Results: The analysis results showed that there was a significant correlation between subtypes using this newly defined classification and overall survival (p < 0.001) and disease‐free survival (DFS) (p < 0.001). Interestingly, patients in the ER+PR−Ki67high subgroup have the worst survival outcome in Luminal B (HER2‐negative) subtype, similar to Triple‐negative patients. Besides, the ER+PR+Ki67high has worse 5‐year DFS compared with Luminal A group. There was a significant relationship between the regrouping subtype and the recurrence score index (RI) (p < 0.001). Moreover, the results showed that patients in ER+PR–Ki67high subtype were more likely to have high RI for distance recurrence (RI‐DR) and local recurrence (RI‐LRR). Our newly defined classification has a better discrimination ability to predict survival outcome and recurrence score of Luminal B (HER2‐negative) BC patients, which may help in clinical decision‐making for individual treatment. [ABSTRACT FROM AUTHOR]

Background: Breast cancer remains the most common malignancy in females around the world. Recently, a growing number of studies have focused on gene dysregulation. In our previous study, Krüppel‐like factors (KLFs) were found to play essential roles in breast cancer development, among which KLF2 could function as a tumor suppressor. Nevertheless, the underlying molecular mechanism remains unclear. Methods: miR‐92a‐3p was identified as the upstream regulator of KLF2 by starBase v.3.0. The regulation of KLF2 by miR‐92a‐3p was verified by a series of in vitro and in vivo assays. Further exploration revealed that Baculoviral IAP Repeat Containing 5 (BIRC5) was the target of KLF2. ChIP assay, dual‐luciferase reporter analysis, quantitative real‐time PCR, and western blot were performed for verification. Results: miR‐92a‐3p functioned as a tumor promoter by inhibiting KLF2 by binding to its 3'‐untranslated region (3'‐UTR). In addition, KLF2 could transcriptionally suppress the expression of BIRC5. Conclusion: Collectively, our results uncovered the miR‐92a‐3p/KLF2/BIRC5 axis in breast cancer and provided a potential mechanism for breast cancer development, which may serve as promising strategies for breast cancer therapy. [ABSTRACT FROM AUTHOR]

Background: X‐ray repair cross‐complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene‐environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction. Methods: The study included 1039 patients with breast cancer and 1040 controls. Four single‐nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene‐environment interactions were analyzed using logistic regression with multiplicative interaction models. Results: XRCC5 rs16855458 was associated with increased breast cancer risk in the co‐dominant (ptrend = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07–1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor‐negative/progesterone receptor‐negative (ER−/PR−) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12–2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (pinteraction = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (pinteraction = 0.0497). However, these interactions became insignificant after Bonferroni correction. Conclusion: XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER−/PR− breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation. [ABSTRACT FROM AUTHOR]

Delta-aminolevulinate dehydratase ( ALAD) catalyzes the second step in the biosynthesis of heme and is also an endogenous inhibitor of the 26S proteasome. The role of ALAD in breast cancer progression is still unclear. In this study, we found that the expression of ALAD was downregulated in breast cancer tissues compared with adjacent normal breast tissues. Enhanced ALAD expression was associated with a favorable outcome in patients with breast cancer. Overexpression of ALAD suppresses breast cancer cell proliferation and invasion and inhibits the epithelial-mesenchymal transition phenotype. Furthermore, we found that ALAD regulates transforming growth factor-β-mediated breast cancer progression. This finding suggests that ALAD might be a potential biomarker for breast cancer that suppresses breast cancer progression by regulating transforming growth factor-β-mediated epithelial-mesenchymal transition. [ABSTRACT FROM AUTHOR]

Serum deprivation response ( SDPR), a key substrate for protein kinase C, play a critical role in inducing membrane curvature and participate in the formation of caveolae. However, the function of SDPR in cancer development and progression is still not clear. Here, we found that SDPR is downregulated in human breast cancer. Overexpression of SDPR suppresses cell proliferation and invasion in MDA- MB-231 cells, while depletion of SDPR promotes cell proliferation and invasion in MCF10A cells. Subsequently, SDPR depletion induces epithelial-mesenchymal transition ( EMT)-like phenotype. Finally, knockdown of SDPR activates transforming growth factor-β ( TGF-β) signaling by upregulation of TGF-β1 expression. In conclusion, our results showed that SDPR inhibits breast cancer progression by blocking TGF-β signaling. Serum deprivation response suppresses cell proliferation and invasion in breast cancer cells. SDPR depletion induces epithelial-mesenchymal transition by activation of TGF-β signaling. [ABSTRACT FROM AUTHOR]

Objectives Micro RNAs (mi RNAs) contribute to control of cell cycle progression and are frequently deregulated in cancer. The focus of this study was to determine effects of miR-142-3p on the cell cycle progression and cancer cell proliferation. Materials and methods RT- qPCR was performed to determine expression of miR-142-3p in a range of cancer cell lines and in clinical cancer specimens. To further understand its role, we restored its expression in cancer cell lines by transfection with miR-142-3p mimics or inhibitors. Effects of miR-142-3p on cell cycle progression and cell proliferation were also determined. Results miR-142-3p was down-regulated in both cancer cell lines and cancer specimens. Its overexpression suppressed proliferation, whereas its depletion promoted it. In addition, miR-142-3p lead to cell cycle arrest in G2/M. Moreover, CDC25C was identified as being a target of miR-142-3p, ectopic expression of which reversed suppression of cell proliferation. Conclusions Our observations suggest that miR-142-3p functioned as a tumor suppressor by targeting CDC25C. [ABSTRACT FROM AUTHOR]

Conventional procedures for the intraoperative assessment of breast cancer sentinel lymph nodes ( SLNs) are frozen section ( FS) and touch imprint cytology ( TIC). The one-step nucleic acid amplification ( OSNA) assay is a novel molecular technique. The aim of this study was to evaluate the optimal approach by comparing OSNA assay, FS, and TIC. Five hundred and fifty-two consecutive patients were enroled from five study centers in China. The SLNs were cut into alternating 2 mm blocks. The odd blocks were tested by the OSNA assay intraoperatively, and the even ones were assessed by postoperative histology (four 4- to 6-μm-thick sections were taken every 200 μm per block). In addition, intraoperative histological assessments were carried out on the even blocks of 211 patients by FS and all blocks of 552 patients by TIC. Overall performance of the assay compared to postoperative histology was: accuracy 91.4%; sensitivity 83.7%; and specificity 92.9%. The sensitivity of the assay was higher than FS (211 patients, 77.6% vs 69.7%; not significant, P = 0.286) and was significantly higher than TIC (552 patients, 83.6% vs 76.2%; P = 0.044). When assessing nodes with micrometastases, the sensitivity of the assay was higher than FS (17 nodes, 47.1% vs 23.5%; not significant, P = 0.289) and was significantly higher than TIC (48 nodes, 62.5% vs 35.4%; P = 0.007). The study indicated that the OSNA assay is an accurate and rapid intraoperative assay for assessing breast SLNs and it can replace FS and TIC for application in general medical practice. The trial was registered as: OSNA assay China Registration Study. Clinical trial registration number: China Breast Cancer Clinical Study Group 001c. [ABSTRACT FROM AUTHOR]