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Circular RNAs (circRNA) have been reported as regulators involved in hepatocellular carcinoma (HCC), but their mechanism of activity remains unknown. This study performed quantitative reverse‐transcription polymerase chain reaction to determine if circNFATC3 was downregulated in 46 paired HCC tissues and cell lines. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, apoptotic, and transwell assay proved that circNFATC3 can inhibit hepatoma cell proliferation, apoptosis, and migration/invasion in vitro. Mouse xenograft assay demonstrated that circNFATC3 suppressed tumor size and weight and reduced lung metastasis in vivo, and vice versa. The RNA‐seq results showed that NFATC3 itself was the most significantly differentially expressed gene when circNFATC3 was manipulated, and bioinformatics and luciferase reporter assays verified circNFATC3 regulated the expression of NFATC3 by interacting with the hsa‐miR‐548I. Additionally, it was also indicated that the level of NFATC3 was downregulated in HCC patients also and was significantly correlated with the staging and prognosis of HCC. Moreover, both circNFATC3 and NFATC3 were shown to inhibit the phosphorylation of JNK, c‐Jun, AKT, and mTOR signaling pathways. Overall, the circNFATC3 can sponge miR‐548I to protect NFATC3 itself, then it regulates hepatoma cell function via the JNK, c‐Jun, AKT, and mTOR signaling pathways, and the circNFATC3 can be a tumor‐repressor on HCC. [ABSTRACT FROM AUTHOR]

When global navigation satellite system (GNSS) receivers move at a high speed, the directions of arrival (DOAs) corresponding to interferences may change rapidly, which will cause a performance degradation of array antenna. A null widening algorithm based on the interference-plus-noise covariance (INC) matrix reconstruction is proposed. Firstly, the number of interferences is estimated via the ratio between adjacent eigenvalues of the sample covariance matrix. Then, the interference DO As are estimated roughly using the spatial spectrum estimates and the spatial spectrum estimates around interferences are reset according to the required null width. Finally, the INC matrix can be reconstructed with the reset spatial spectrum estimates, based on which the weight vector is sloved. Simulation results show that the proposed algorithm performs better than the other null widening algorithms in the carrier to noise ratio (C/No), by at least 5 dBHz. Meanwhile, the proposed algorithm has a deeper null when the null width keeps the same. [ABSTRACT FROM AUTHOR]

In order to solve the blind estimation problem of the frequency hopping (FH) parameters in the complex electromagnetic environment, an algorithm based on time-frequency variance clustering is proposed. Considering the case where both low signal-to-noise ratio (SNR) and fixed frequency interference exist simultaneously, the signal is transformed into the time-frequency domain by short-time Fourier transform (STFT). The time-frequency interval of the signal is extracted by genetic algorithm, and k-means clustering is performed according to the time-frequency variance. Eliminating noise and fixed-frequency interference, and then extracting time-frequency ridge, the Haar wavelet is used to detect its singularities, furthermore, to estimate parameters such as FH period, hopping speed and hopping frequency. The simulation results show that the proposed algorithm can accurately estimate the parameters such as FH period when the SNR is lower than -5 dB. The correct probability of parameter estimation is over 90%. [ABSTRACT FROM AUTHOR]

The present study aimed at evaluating the mechanism by which functionality of hepatic stellate cells (HSCs) is modulated by bone marrow stromal cells (BMSCs). Induction of apoptosis in HSCs was found to be caused by directly co-culturing HSCs with BMSCs, where the expression of α-smooth muscle actin (α-SMA) increased significantly in HSCs, along with an increase in their proliferation rate. Additionally, expression of Hes1 and Notch1 in HSCs co-cultured with BMSCs increased significantly at both protein and mRNA levels. Blocking of the notch signaling pathway (NSP) either by Notch1 siRNA or by DAPT treatment increased the proliferation rate while decreasing apoptosis and led to activation of the NF-κB signaling pathway in HSCs co-cultured with BMSCs. These effects were found to be reversed in HSCs overexpressing IκB S32/S36 mutants. The Notch signaling-mediated cell-cell contact was partially involved in the significant inhibition of proliferation of HSCs by BMSCs. Additionally, the NF-κB pathway was found to be responsible for NSP-mediated inhibition of growth of HSCs in the co-culture system. Thus, BMSCs might have a potential therapeutic significance in treating hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumours, including non‐small cell lung cancer (NSCLC). However, the underlying molecular mechanisms of their specific association with NSCLC have not been fully elucidated. Here, we report that a cytoplasmic lncRNA, DUXAP9‐206 is overexpressed in NSCLC cells and closely related to NSCLC clinical features and poor patient survival. We reveal that DUXAP9‐206 induced NSCLC cell proliferation and metastasis by directly interacting with Cbl‐b, an E3 ubiquitin ligase, and reducing the degradation of epidermal growth factor receptor (EGFR) and thereby augmenting EGFR signaling in NSCLC. Notably, correlations between DUXAP9‐206 and activated EGFR signaling were also validated in NSCLC patient specimens. Collectively, our findings reveal the novel molecular mechanisms of DUXAP9‐206 in mediating the progression of NSCLC and DUXAP9‐206 may serve as a potential target for NSCLC therapy. [ABSTRACT FROM AUTHOR]

Glioblastoma are among the most common forms of cancer affecting the central nervous system, and yet there is currently no effective means of treating them. In the current study, we reported that tousled-like kinase 2 (TLK2) is a key factor in glioblastoma that modulates SRC signaling, thereby driving tumor malignancy. TLK2 is commonly upregulated in glioblastoma, and such upregulation was associated with poor patient outcomes. TLK2 overexpression induced cell growth, migration, invasion, and epithelial-mesenchymal transition, and cell cycle arrest, while TLK2 knockdown had the opposite effect. SRC pathway inhibition by Saracatinib resulted in reduced TLK2-mediated glioblastoma migration, invasion, confirming a key role for SRC signaling in regulating the functions of TLK2. Together, our findings demonstrate that glioblastoma TLK2 overexpression acts as a key driver of tumor malignancy via SRC signaling pathway. [ABSTRACT FROM AUTHOR]

There is increasing evidence that circular RNA (circ RNA) are involved in cancer development, but the regulation and function of human circ RNA remain largely unknown. In this study, we demonstrated that ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular ( circ ZKSCAN1) forms of RNA in human hepatocellular carcinoma ( HCC) tissues and cell lines. Here, we analyzed a cohort of 102 patients and found that expression of both ZKSCAN1 mRNA and circ ZKSCAN1 was significantly lower ( P < 0.05) in the HCC samples compared with that in matched adjacent nontumorous tissues by reverse transcription PCR ( RT- PCR). The low expression level of ZKSCAN1 was only associated with tumor size ( P = 0.032), while the cir ZKSCAN1 levels varied in patients with different tumor numbers ( P < 0.01), cirrhosis ( P = 0.031), vascular invasion ( P = 0.002), or microscopic vascular invasion ( P = 0.002), as well as with the tumor grade ( P < 0.001). Silencing both ZKSCAN1 mRNA and circ ZKSCAN1 promoted cell proliferation, migration, and invasion. In contrast, overexpression of both forms of RNA repressed HCC progression in vivo and in vitro. Silencing or overexpression of both forms of RNA did not interfere with each other. RNA-seq revealed a very different molecular basis for the observed effects; ZKSCAN1 mRNA mainly regulated cellular metabolism, while circ ZKSCAN1 mediated several cancer-related signaling pathways, suggesting a nonredundant role for ZKSCAN1 mRNA and circ RNA. In conclusion, our results revealed two post-translational products ( ZKSCAN1 mRNA and circ ZKSCAN1) that cooperated closely with one another to inhibit growth, migration, and invasion of HCC. cir ZKSCAN1 might be a useful marker for the diagnosis of HCC. [ABSTRACT FROM AUTHOR]