tsRNA: A Promising Biomarker in Breast Cancer.

tRNA-derived small RNAs (tsRNAs) are a novel class of non-coding small RNAs, generated from specific cleavage sites of tRNA or pre-tRNA. tsRNAs can directly participate in RNA silencing, transcription, translation, and other processes. Their dysregulation is closely related to the occurrence and development of various cancers. Breast cancer is one of the most common and fastest-growing malignant tumors in humans. tsRNAs have been found to be dysregulated in breast cancer, serving as a new target for exploring the pathogenesis of breast cancer. They are also considered new tumor markers, providing a basis for diagnosis and treatment. This article reviews the generation, classification, mechanism of action, function of tsRNAs, and their biological effects and related mechanisms in breast cancer, in the hope of providing a new direction for the diagnosis and treatment of breast cancer.

Metabolism-regulating non-coding RNAs in breast cancer: roles, mechanisms and clinical applications.

Breast cancer is one of the most common malignancies that pose a serious threat to women's health. Reprogramming of energy metabolism is a major feature of the malignant transformation of breast cancer. Compared to normal cells, tumor cells reprogram metabolic processes more efficiently, converting nutrient supplies into glucose, amino acid and lipid required for malignant proliferation and progression. Non-coding RNAs(ncRNAs) are a class of functional RNA molecules that are not translated into proteins but regulate the expression of target genes. NcRNAs have been demonstrated to be involved in various aspects of energy metabolism, including glycolysis, glutaminolysis, and fatty acid synthesis. This review focuses on the metabolic regulatory mechanisms and clinical applications of metabolism-regulating ncRNAs involved in breast cancer. We summarize the vital roles played by metabolism-regulating ncRNAs for endocrine therapy, targeted therapy, chemotherapy, immunotherapy, and radiotherapy resistance in breast cancer, as well as their potential as therapeutic targets and biomarkers. Difficulties and perspectives of current targeted metabolism and non-coding RNA therapeutic strategies are discussed.

A comprehensive evaluation of circ_0065214/ miR-188-3p/GPNMB axis in breast cancer.

CircRNAs are involved in multiple aspects during carcinogenesis, including tumorigenesis, vascularization, apoptosis and others. Exploring the role of circRNAs in breast cancer (BC) enables us to understand the development mechanism of BC more comprehensively. Here, we screened out and verified an up-regulated circRNA in BC from GEO data. Quantitative Real-time PCR (qRT-PCR) showed that circ_0065214 had a high expression level in BC patients. Besides, circ_0065214 had good diagnostic value in BC serum, and the area under the diagnostic curve, sensitivity and specificity were 0.78, 0.63 and 0.85, respectively. The combined application of circ_0065214 with CEA and CA-153 can further improve the diagnostic efficiency. The knockdown of circ_0065214 in vivo and in vitro inhibited the proliferation, migration and invasion of BC, but promoted autophagy. At last, dual-luciferase reporter assay and rescue assays revealed that circ_0065214 acted as a decoy to adsorb miR-188-3p, and then relieved the repressive effect of miR-188-3p on its target GPNMB. Our results demonstrated that circ_0065214 regulated the expression of GPNMB by competitively binding to miR-188-3p, thus promoting the proliferation, migration and invasion of breast cancer cells and inhibiting autophagy. These findings provided an original therapeutic strategy for BC.

OAMDP, a novel podophyllotoxin derivative, induces apoptosis, cell cycle arrest and autophagy in hepatoma HepG2 cells.

4ß-(1,3,4-oxadiazole-2-amino-5-methyl)-4-deoxypodophyllotoxin (OAMDP), a novel podophyllotoxin derivative, has demonstrated potent anti-tumor activity with significant cytotoxic effect. Here, we report the anti-proliferative effect of OAMDP, for which OAMDP could suppress the proliferation of HepG2 cells (human hepatoma cell line) in a dose- and time-dependent manner. After treating with OAMDP, cell apoptosis was confirmed by Annexin V-FITC/PI double staining assay. Furthermore, flow cytometry analysis revealed the loss of mitochondrial membrane potential and the increase of intracellular reactive oxygen species in HepG2 cells. OAMDP increased apoptotic cell population with induction of Bax, cytochrome c (cyt-c), caspase-9, caspase-3, PARP1 and the reduction of Bcl-2 and p-Akt protein expressions. The MAPK family, JNK, ERK, p38, p-JNK, p-ERK, p-p38, were also regulated by OAMDP in HepG2 cells. Moreover, cell cycle analysis showed that OAMDP induced S or G2/M phase arrest through modulation of cycle regulatory proteins. In addition, MDC staining and LC3 protein expression indicated that autophagy was induced by OAMDP in HepG2 cells. To sum up, our results suggested that OAMDP, with the ability to induce autophagy, causing cell cycle arrest and apoptosis, has potential to become a novel anti-tumor agent.

Full-Duplex Cooperative Sensing for Spectrum-Heterogeneous Cognitive Radio Networks.

In cognitive radio networks (CRNs), spectrum sensing is critical for guaranteeing that the opportunistic spectrum access by secondary users (SUs) will not interrupt legitimate primary users (PUs). The application of full-duplex radio to spectrum sensing enables SU to carry out sensing and transmission simultaneously, improving both spectrum awareness and CRN throughput. However, the issue of spectrum sensing with full-duplex radios deployed in heterogeneous environments, where SUs may observe different spectrum activities, has not been addressed. In this paper, we give a first look into this problem and develop a light-weight cooperative sensing framework called PaCoSIF, which involves only a pairwise SU transmitter (SU-Tx) and its receiver (SU-Rx) in cooperation. A dedicated control channel is not required for pairwise cooperative sensing with instantaneous feedback (PaCoSIF) because sensing results are collected and fused via the reverse channel provided by full-duplex radios. We present a detailed protocol description to illustrate how PaCoSIF works. However, it is a challenge to optimize the sensing performance of PaCoSIF since the two sensors suffer from spectrum heterogeneity and different kinds of interference. Our goal is to minimize the false alarm rate of PaCoSIF given the bound on the missed detection rate by adaptively adjusting the detection threshold of each sensor. We derive an expression for the optimal threshold using the Lagrange method and propose a fast binary-searching algorithm to solve it numerically. Simulations show that, with perfect signal-to-interference-and-noise-ratio (SINR) information, PaCoSIF could decrease the false alarm rate and boost CRN throughput significantly against conventional cooperative sensing when SUs are deployed in spectrum-heterogeneous environments. Finally, the impact of SINR error upon the performance of PaCoSIF is evaluated via extensive simulations.