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microRNAs are a small class of non-coding RNAs with a critical role in the tumorigenesis and maintenance of breast cancer through binding to the 3'-untranslated regions of target mRNAs, which causes a block of translation and/or mRNA degradation. The purpose of this study was to investigate the expression of microRNA-497 (miR-497) as well as its potential role in human breast cancer. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to determine the expression pattern of miR-497 in breast cancer and normal breast tissues. Correlation analysis was conducted to characterize the association of miR-497 expression abnormality with pathological factors. Proliferation, cell cycle and apoptosis assays were conducted to explore the potential function of miR-497 in human MCF-7 breast cancer cells. RT-PCR and Western blot analysis were employed to validate the downstream targets of miR-497. miR-497 expression was relatively decreased in breast cancer specimens and negatively correlated with TNM stage, lymphatic metastasis, tumor size and human epidermal growth factor receptor-2 (P<0.01). On the contrary, no correlation was found with estrogen receptor, progesterone receptor and p53 status. Functional assays revealed that miR-497 suppressed cellular growth, increased the percentage of early apoptotic cells and initiated G0/G1 cell phase arrest of MCF-7 cancer cells. RT-PCR and Western blot analysis data indicated that the overexpression of miR-497 resulted in the down-regulation of Bcl-w at the mRNA and protein levels. miR-497 may serve as a tumor suppressor gene in breast cancer. The Up-regulation of miR-497 expression causes cellular growth inhibition and apoptotic enhancement, as well as G0/ G1 phase arrest, suggesting its use as a potential therapeutic target for the treatment of breast cancer in the future.

Background: Long noncoding RNAs have been known to be involved in multiple types of malignancies, including invasive breast cancer (IBC). This study aimed to explore the role of long noncoding RNAs in IBC and elucidate the potential molecular mechanisms. Methods: Using TCGA microarray data analysis, we identified a long noncoding RNA, MIR210HG, highly expressed in IBC. Kaplan-Meier method and the log-rank test were used for survival analysis. The gain-of-function experiments were performed to assess the function of MIR210HG in IBC invasion and migration in both in vitro and in vivo settings. Bioinformatic analysis as well as luciferase reporter assay, rescue experiments and western blot assay revealed the mode of action of MIR210HG. Results: The aberrantly enhanced MiR210HG expression predicted poor prognosis and lower survival rate. Knockdown of MiR210HG suppressed IBC cell invasion and metastasis both in vitro and in vivo . MiR-1226-3p was identified and validated to be the target miRNA of MiR210HG. Furthermore, MiR210HG functions as a competing endogenous RNAs (ceRNA) which sponges miR-1226-3p, therefore upregulates the expression of mucin1 (MUC1-C). Conclusions: Our study demonstrated that MiR210HG sponges miR-1226-3p to facilitate invasive breast cancer cell invasion and metastasis by regulating mucin-1c and EMT pathway, revealing the oncogenic role of MiR210HG in IBC cells.

Dysregulation of microRNAs (miRNAs) plays a critical role in cancer progression. They can act as either oncogenes or tumor suppressor genes in human cancer. The purpose of this study was to investigate the crucial role of miR-135b in breast cancer and to validate whether miR-135b could regulate proliferation of breast cancer cells by effecting specific targets in the Hippo pathway. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was carried out to quantify the expression levels of miR-135b in both breast cancer tissues and cell lines. To characterize the function of miR-135b, MTT assays, colony formation assays, cell migration assays, cell invasion assays, and cell cycle assays were used. Luciferase reporter assays were performed to validate the regulation of a putative target of miR-135b, in corroboration with western blot assays. Finally, we verified the changes of cellular function after transfection of LATS2-siRNA. Our experiments indicate that expression of miR-135b was commonly upregulated in breast cancer specimens and breast cancer cells when compared with that in adjacent normal tissues and non-malignant breast epithelial cells. Enforced expression of miR-135b can regulate cellular proliferation, migration and invasion as well as disrupt the cell cycle of breast cancer cells. Luciferase assays revealed that miR-135b directly bound to the 3'-untranslated region (3'-UTR) of LATS2 (large tumor suppressor kinase 2), a critical gene in the Hippo pathway. Western blot analysis verified that miR-135b regulated the expression of LATS2 at protein levels. Further study demonstrated that the downstream gene of LATS2 in the Hippo pathway, such as cyclin-dependent kinase 2 (CDK2) and Phospho-Yes-associated protein (p-YAP), can also be regulated by miR-135b and LATS2 axis. Knockdown of endogenous LATS2 can mimic the result of miR-135b up-regulation in breast cancer. Taken together, our findings reveal that the miR-135b and LATS2 axis may be a potential therapeutic target for breast cancer in the future.

Triple-negative breast cancer (TNBC) has the worst prognosis of all subtypes of breast cancer (BC), with limited options for conventional therapy and no targeted therapies. MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression. In this study, we aimed to determine whether two members of the miR-200 family, miR-200b-3p and miR-429-5p, are involved in BC cell proliferation and motility and to elucidate their target genes and pathways. We performed a meta-analysis that reveals down-regulated expression of miR-200b-3p and miR-429-5p in BC tissues and cell lines, consistent with a lower expression of miR-200b-3p and miR-429-5p in MDA-MB-231 and HCC1937 cells than in MCF-7 and MCF-10 cells. Overexpression of miR-200b-3p and miR-429-5p significantly inhibited the proliferation, migration, and invasion of TNBC cells; suppressed the expression of markers for proliferation and metastasis in TNBC cells. We next demonstrated that LIM domain kinase 1 (LIMK1) is a direct target gene of miR-200b-3p and miR-429-5p. Inhibition of LIMK1 reduced the expression and phosphorylation of cofilin 1 (CFL1), which polymerizes and depolymerizes F-actin and G-actin to reorganize cellular actin cytoskeleton. In addition, transfection with mimics for miR-200b-3p and miR-429-5p arrested G2/M and G0/G1 cell cycles respectively, suppressed the expression of the cell cycle–related complexes, cyclin D1/CDK4/CDK6 and cyclin E1/CDK2, in TNBC cells. In conclusion, miR-200b-3p and miR-429-5p suppress proliferation, migration, and invasion in TNBC cells, via the LIMK1/CFL1 pathway. These results provide insight into how specific miRNAs regulate TNBC progression and suggest that the LIMK1/CFL1 pathway is a therapeutic target for treating TNBC.

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Model predictive control (MPC) has been studied in the building science realm for about three decades. However, the following two aspects of the building control have not been studied thoroughly in MPC research. One is the impact of the mixed-mode cooling system on the active heating ventilation and air conditioning (HVAC) energy consumption, and the other is the differences of individual thermal comfort preference and its impact on energy. This paper proposes an occupant-oriented mixed-mode EnergyPlus predictive control system to optimize HVAC energy consumption while meeting the individual thermal comfort preference. A web-based dashboard is implemented in the test-bed building for three months to collect individual thermal comfort preference data. The data analysis results suggest that occupants have various tolerances and preferences about thermal comfort. The simulation results show that, during one week of a typical swing season, the mixed-mode system further reduces the active HVAC energy consumption, and the diversified occupant thermal comfort preference has significant impact on HVAC energy consumption.