Cyclin D1-mediated microRNA expression signature predicts breast cancer outcome

Background: Genetic classification of breast cancer based on the coding mRNA suggests the evolution of distinct subtypes. Whether the non-coding genome is altered concordantly with the coding genome and the mechanism by which the cell cycle directly controls the non-coding genome is poorly understood. Methods: Herein, the miRNA signature maintained by endogenous cyclin D1 in human breast cancer cells was defined. In order to determine the clinical significance of the cyclin D1-mediated miRNA signature, we defined a miRNA expression superset from 459 breast cancer samples. We compared the coding and non-coding genome of breast cancer subtypes. Results: Hierarchical clustering of human breast cancers defined four distinct miRNA clusters (G1-G4) associated with distinguishable relapse-free survival by Kaplan-Meier analysis. The cyclin D1-regulated miRNA signature included several oncomirs, was conserved in multiple breast cancer cell lines, was associated with the G2 tumor miRNA cluster, ERα+ status, better outcome and activation of the Wnt pathway. The coding and non-coding genome were discordant within breast cancer subtypes. Seed elements for cyclin D1-regulated miRNA were identified in 63 genes of the Wnt signaling pathway including DKK. Cyclin D1 restrained DKK1 via the 3\u27UTR. In vivo studies using inducible transgenics confirmed cyclin D1 induces Wnt-dependent gene expression. Conclusion: The non-coding genome defines breast cancer subtypes that are discordant with their coding genome subtype suggesting distinct evolutionary drivers within the tumors. Cyclin D1 orchestrates expression of a miRNA signature that induces Wnt/β-catenin signaling, therefore cyclin D1 serves both upstream and downstream of Wnt/β-catenin signaling

Small RNA zippers lock miRNA molecules and block miRNA function in mammalian cells.

MicroRNAs (miRNAs) loss-of-function phenotypes are mainly induced by chemically modified antisense oligonucleotides. Here we develop an alternative inhibitor for miRNAs, termed \u27small RNA zipper\u27. It is designed to connect miRNA molecules end to end, forming a DNA-RNA duplex through a complementary interaction with high affinity, high specificity and high stability. Two miRNAs, miR-221 and miR-17, are tested in human breast cancer cell lines, demonstrating the 70∼90% knockdown of miRNA levels by 30-50 nM small RNA zippers. The miR-221 zipper shows capability in rescuing the expression of target genes of miR-221 and reversing the oncogenic function of miR-221 in breast cancer cells. In addition, we demonstrate that the miR-221 zipper attenuates doxorubicin resistance with higher efficiency than anti-miR-221 in human breast cancer cells. Taken together, small RNA zippers are a miRNA inhibitor, which can be used to induce miRNA loss-of-function phenotypes and validate miRNA target genes

SLA-based online charging model in mobile environment

The objective of this paper is to provide a specialised online charging model in order to make use of Service Level Agreement (SLA) characteristics in a mobile telecommunication environment. The proposed model is based on the service enablers concepts in mobile internet environment (related to OMA and 3GPP standards), and termed as SLA-OC model. The Service Level Agreement (SLA) characteristics comprise of Operator's characteristics such as security and channel QoS, and Service Provider's characteristics such as service content. So the SLA-OC model will combine the Operator's value and Service Provider's value together, and will guarantee accurate payment for customers of different level SLA. The paper describes the SLA-OC model elements and policies, and show how these characteristics can be translated into quantitive elements. It also involves the prototype of SLA-OC model, based on the industrial tools of 'ECharts for SIP Servlets' and 'SailFin'. The model's prototype is applicable in telecommunication industry

Modeling based-on semi-tensor product for the start-up stage of the radiant cooling system

For nonlinear systems with multiple outputs and multiple inputs which cannot be decoupled, we make use of the sampling data of the real system to obtain a fuzzy relation matrix model via the semi-tensor product (STP) operation of matrices, and establish the mathematical model for a complicated system based on STP. This method has been applied to analyze the dynamic performance of floor for the radiant floor system. In this paper, a radiant floor cooling system based on concrete core radiant floors is examined. To analyze dynamic behaviour of floors during non working time operation, model of fuzzy relation matrix based on STP is established. The model is used to estimate quantitativelyrelated parameters in the start-up period of the floor systems under the impact of outdoor environment such as temperature and humidity during the actual cool-down times. The results show that it is not evident to time delay of the floor surface temperature and indoor air temperature due to the thermal inertia while the amplitude of outdoor air temperature vibration is reduced significantly

Wireless mobile-based shopping mall car parking system (WMCPS)

The existing car parking system in Malaysia usually required the car drivers to search an empty parking space in the car park without providing detail direction toward the available parking space. As the result, drivers may waste a lot of time and unnecessary energy while they turn around in the car park without direction and may cause car traffic congestion in parking space. This paper investigates the problems of car parking system in Malaysia and finally proposed a Wireless Mobile-based Car Parking System using low cost SMS service. The implementation of SMS service into the car parking system enable drivers to receive information regarding the availability of car parking spaces. In this system, the drivers can resend SMS to request for new assignment of car parking spaces if they fail to get the previous assigned destination. This paper demonstrates the design and implementation of Wireless Mobile-based Car Parking System (WMCPS) using SMS services by Breadth First Search (BFS) algorithm in finding the nearest parking space for drivers. The stimulation results reveal the intelligence of this system can efficiently allocate and utilize the car parking spaces inside the car park

A direct quantification method for measuring plasma MicroRNAs identified potential biomarkers for detecting metastatic breast cancer.

Circulating miRNAs are protected from ribonuclease degradation by assembly into microvesicles and exosomes. Releasing miRNAs completely from these particles is the key step to quantify the circulating miRNAs. Currently purified RNA-based quantitative analysis is widely used while it is time and cost consuming with high risk for those circulating miRNAs with low abundance due to partial loss of RNA during the steps of total RNA extraction and small RNA enrichment. Herein, we optimized a simple, effective and time-saving method to directly measure plasma miRNAs without RNA isolation. It is based on complete miRNA release from the protein complexes, followed by miRNA-specific reverse transcription and quantitative real-time PCR amplification. By comparison to the RNA-based approach, the direct quantification method showed more efficiency for circulating miRNA analysis, higher accuracy and specificity. By application of the direct quantification method to clinical samples combined with the RNA-based miRNA screening analysis, upregulation of miR-106a in blood was validated in metastatic breast cancer patients, indicating miR-106a are a potential biomarker for metastatic breast cancer