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Tamoxifen is still the most commonly used endocrine therapy drug for estrogen receptor (ER)-positive breast cancer patients and has an excellent outcome, but tamoxifen resistance remains a great impediment to successful treatment. Recent studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF-7, especially when combined with tamoxifen, but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the expression of these proteins in the resistant cell line. When knocking down c-myc in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to overcome tamoxifen resistance. Our study discovered a novel role of aspirin based on its anti-tumor effect, and put forward some kinds of possible mechanisms of tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy for the treatment of ER-positive breast carcinoma.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, could lead to kinds of clinical disorders and remains a leading global health problem, resulting in great morbidity and mortality worldwide. Previous studies have firmly demonstrated that M. tuberculosis (M.tb) has evolved to utilize different mechanisms to evade or attenuate the host immune response, such as regulation of immune-related genes by modulation of miRNAs of host or bacteria. However, the knowledge of functions of miRNAs during M.tb infection remains limited. Here, we reported that a host microRNA, miR-125a, was significantly up-regulated by M.tb infection in both RAW264.7 and THP-1cells, in a TLR4 signaling-dependent manner. Subsequently, our results demonstrated that miR-125a was a negative regulator of NF-kB pathway by directly targeting TRAF6, resulting in the suppression of cytokines, attenuation of immune response and promotion of M.tb survival. Taken together, our findings provide a novel detailed molecular mechanism in which miR-125a was enhanced to inhibit inflammatory cytokines secretion and attenuate the immune response during M.tb infection in RAW264.7 and THP-1 cells, and suggest an intrinsic a promising anti-M.tb therapeutic target.

Serum circulating microRNAs (c‐miRNAs) are serving as useful biomarkers for cancer diagnosis. Here, we describe the development of a one‐step branched rolling circle amplification (BRCA) method to measure serum c‐miRNAs levels for early diagnosis of breast cancer. Four c‐miRNAs, c‐miRNA16 (c‐miR‐16), c‐miRNA21 (c‐miR‐21), c‐miRNA155 (c‐miR‐155), and c‐miRNA195 (c‐miR‐195) were isolated from the serum of 49 breast cancer patients (stages I‐IV) and 19 healthy controls, and analyzed using one‐step BRCA. The serum levels of c‐miR16, c‐miR21, c‐miR155, and c‐miR195 were higher (P < 0.0001) in stage I breast cancer patients than healthy controls. These levels were also higher in several breast cancer molecular subtypes (HER‐2 over‐expression, Luminal A, Luminal B, and triple negative breast cancer) than in healthy control subjects. The diagnostic accuracy of c‐miR16, c‐miR21, c‐miR155, and c‐miR195 for early diagnosis of breast cancer was confirmed by receiver operating characteristic (ROC) curve assay. These results show that the BRCA method can be used to measure serum c‐miRNAs levels, and that this method has high accuracy, sensitivity, and specificity. Moreover, both BRCA approach and quantitative real‐time PCR (qRT‐PCR) method show that the serum levels of c‐miR16, c‐miR21, c‐miR155, and c‐miR195 could be used as biomarkers to improve the early diagnosis of breast cancer, and distinguish different breast cancer molecular subtypes.

Purpose: Neoadjuvant chemotherapy (NACT) is increasingly adopted in the therapy of breast cancer (BC) patients with positive axillary nodes (cNþ), but the reliability and feasibility of sentinel lymph node biopsy (SLNB) following NACT are still controversial. The objective of the present study is to conduct an updated meta-analysis on this issue. Methods: A literature search was performed using PubMed, Cochrane, Embase, and Web of Science to identify papers published from January 1, 2000 to October 22, 2020 to research SLNB after NACT in BC patients. Studies that met the quality standard were enrolled for this meta-analysis. Results: A total of 3578 participants from 27 trials were included in this meta-analysis. The pooled estimate of the identification rate (IR) for SLNB was 91 %, and the false negative rate (FNR) was 15 %. The pooled negative prediction value (NPV), accuracy, specificity, and sensitivity were 82 %, 89 %, 97 %, and 85 %, respectively. In subgroup analysis, the application of dual mapping could clearly decrease the FNR. The FNR was significantly high in the luminal types, and it declined as more sentinel lymph nodes (SLNs) were removed. Conclusion: SLNB following NACT is now technically feasible for BC with cNþ. However, it must be emphasized that the FNR is unacceptable high.

The homeobox (HOX) genes, a class of transcription factors, are known to promote embryonic development and induce tumor formation. To date, the HOXA and HOXB gene families have been reported to be associated with breast cancer. However, the expression and exact role of homeobox C13 (HOXC13) in breast cancer has not yet been investigated. In the present study, the HOXC13 expression in human breast cancer was evaluated using the Oncomine database and Cancer Cell Line Encyclopedia (CCLE). Next, the Gene expression-based Outcome for Breast cancer online database, cBioportal, University of California Santa Cruz Xena browser and bc-GenExMinerv were used to explore the specific expression of HOXC13 in breast cancer. The methylation and mutation status of HOXC13 in breast cancer was then validated using the CCLE and cBioportal databases. Finally, the co-expression of HOX transcript antisense RNA (HOTAIR) and HOXC13 in breast cancer were analyzed and their impact on clinical prognosis determined. It was found that the expression of HOXC13 was high in breast cancer compared with other types of cancer, such as gastric cancer and colon cancer. Following co-expression analysis, a significant positive association was identified between HOTAIR and HOXC13. An association between HOTAIR and HOXC13, and lymph node and distant metastasis recurrence was also revealed during the development of breast cancer. Of note, survival analysis showed that high expression of HOTAIR and HOXC13 predicted poor prognosis. These findings revealed that HOXC13 plays an important role in the progression of breast cancer. However, the specific mechanism needs to be confirmed by subsequent experiments.

Abstract. Previous studies have reported that breast cancer stem cells may be closely associated with tumor metastasis, recurrence, and even the failure of chemotherapy and radiotherapy. The aim of the present study was to investigate whether important cell signaling pathways associated with drug resistance are activated in stem-like acetaldehyde dehydrogenase (ALDH)

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