lncRNA MIR4435­2HG promotes the progression of liver cancer by upregulating B3GNT5 expression.

Several studies have indicated that dysregulation of long non­coding RNAs (lncRNAs) participates in the initiation and progression of cancer. The lncRNA MIR4435­2HG was previously reported to act as an oncogene in human cancer, including liver cancer. However, its role in the pathogenesis in liver cancer is largely unclear. The present study aimed to reveal the molecular mechanism by which MIR4435­2HG regulates liver cancer. The expression levels of MIR4435­2HG in liver cancer and adjacent normal tissues were analyzed using The Cancer Genome Atlas database. MIR4435­2HG expression was validated by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) in cancer cells in vitro. The target genes of MIR4435­2HG were predicted using bioinformatics analysis. Interactions between miR­136­5p, MIR4435­2HG and B3GNT5 were detected using luciferase reporter assays, and their effects on cell viability, migration and invasion were assessed using Cell Counting Kit­8, wound healing and Transwell assays. The effects of miR­136­5p and MIR4435­2HG on B3GNT5 expression were confirmed by western blot analysis. The results revealed that MIR4435­2HG expression was upregulated in primary liver cancer and liver cancer cell lines, and was positively associated with advanced tumor stage, metastasis and poor prognosis in patients with liver cancer. Knockdown of MIR4435­2HG significantly inhibited the proliferation, migration and invasion of liver cancer cells. Furthermore, miR­136­5p was determined to be a direct target of MIR4435­2HG and suppressed MIR4435­2HG expression by binding with the seed region of the 3'­UTR of MIR4435­2HG in liver cancer cells. Functional studies showed that the inhibitory effects of MIR4435­2HG knockdown on cell proliferation, migration and invasion were significantly rescued by inhibiting miR­136­5p. Furthermore, the target gene, B3GNT5, of miR­136­5p was confirmed by bioinformatics analysis and RT­qPCR. In addition, B3GNT5 expression was regulated by the MIR4435­2HG/miR­136­5p axis. In conclusion, the present study indicated that MIR4435­2HG facilitated the progression of liver cancer via the MIR4435­2HG/miR­136­5p/B3GNT5 axis, which demonstrated that MIR4435­2HG may be a potential biomarker for the prognosis and treatment of liver cancer.

The emerging landscape of long non-coding RNAs in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers. HCC shows high prevalence and lethality caused by a variety of etiologic factors. However, the underlying mechanisms and the diagnostic markers identifying patients at risk in advance has not been entirely elucidated. Long non-coding RNAs (lncRNAs) are a subgroup of non-coding RNAs greater than 200 nucleotides in length with no protein-coding capability. With the progress in sequencing technologies and bioinformatic tools, the landscape of lncRNAs is being revealed. Numerous discoveries point out that lncRNAs participate in HCC carcinogenesis and metastasis through altering cell proliferation and invasion ability, apoptosis, and chemo- or radio-sensitivity. Moreover, lncRNA is easy to detect compared to the traditional diagnostic methods. This review summarizes the mechanisms of major lncRNAs in HCC discovered in recent years and lncRNAs as early diagnostic markers for HCC.

Knockdown of long noncoding RNA colorectal neoplasia differentially expressed inhibits hepatocellular carcinoma progression by mediating the expression of nuclear autoantigenic sperm protein.

Long noncoding RNAs (lncRNAs) play critical roles in the tumorigenesis and progression of hepatocellular carcinoma (HCC). As the most common malignant cancer type in humans, HCC poses a great threat to human health. However, the function of lncRNA colorectal neoplasia differentially expressed (CRNDE) in HCC has not been extensively studied. The chief aim of the present study was to reveal the potential role of CRNDE in HCC. Expression levels of CRNDE in HCC tissues and cell lines were detected by reverse transcription­quantitative (RT­q) PCR, and Cell Counting kit 8, wound­healing and Transwell assays were used to evaluate the influences of CRNDE on in vitro cellular proliferation, migration and invasiveness, respectively. The interaction between CRNDE and microRNA (miR)­29c­3p was determined by dual­luciferase reporter assay, and rescue experiments were conducted to evaluate the interactive relationships between CRNDE and miR­29c­3p or nuclear autoantigenic sperm protein (NASP). CRNDE was found to be upregulated in HCC tissues and cells, and to be positively associated with the poor prognosis of patients with HCC. Furthermore, CRNDE­knockdown suppressed cell proliferation, migration and invasion abilities. Bioinformatics and RT­qPCR analysis indicated miR­29c­3p as a potential target of CRNDE. In line with previous reports, as a tumor suppressor, downregulated expression of miR­29c­3p was observed in HCC. In addition, the present study revealed that miR­29c­3p directly targeted NASP. NASP expression was markedly elevated following transfection with an miR­29c­3p inhibitor, while knocking down CRNDE inhibited NASP expression. Moreover, the effects of CRNDE and NASP on HCC cells were reversed by miR­29c­3p. Collectively, the results of the present study revealed that CRNDE was upregulated and exerted an oncogenic role in HCC by targeting miR­29c­3p, and that the upregulation of CRNDE also promoted NASP expression. These findings indicate a novel role for CRNDE in the progression of HCC.

Exosome-derived microRNA-433 inhibits tumorigenesis through incremental infiltration of CD4 and CD8 cells in non-small cell lung cancer.

Tumor-derived exosomal microRNAs (miRNAs/miRs) serve a vital biological role in tumorigenesis and development, but the effects and underlying mechanisms remain unclear. To explore the impact of exosomal miR-433 in non-small cell lung cancer (NSCLC) and understand its mechanism of action in NSCLC progression, the present study isolated the exosomes from the plasma of patients with NSCLC after chemotherapy and found that miR-433 expression was lower in plasma of patients with resistant NSCLC compared with in plasma of patients with sensitive NSCLC and in normal serum. Additionally, miR-433 expression was markedly negatively associated with a large tumor size, distant metastasis, advanced TNM stage and a poor prognosis in patients with NSCLC. miR-433 inhibited tumor growth by blocking the cell cycle in vitro and in vivo, as well as by promoting apoptosis and T-cell infiltration in the tumor microenvironment. Additionally, miR-433 inhibited chemoresistance to cisplatin by regulating DNA damage. Moreover, miR-433 inactivated the WNT/ß-catenin signaling pathway by targeting transmembrane p24 trafficking protein 5 in NSCLC. Overall, the current findings may provide a potential prognostic biomarker and therapeutic target for patients with NSCLC.

A novel optimal multi-pattern matching method with wildcards for DNA sequence.

BACKGROUND: DNA sequence alignment is one of the most fundamental and important operation to identify which gene family may contain this sequence, pattern matching for DNA sequence has been a fundamental issue in biomedical engineering, biotechnology and health informatics. OBJECTIVE: To solve this problem, this study proposes an optimal multi pattern matching with wildcards for DNA sequence. METHODS: This proposed method packs the patterns and a sliding window of texts, and the window slides along the given packed text, matching against stored packed patterns. RESULTS: Three data sets are used to test the performance of the proposed algorithm, and the algorithm was seen to be more efficient than the competitors because its operation is close to machine language. CONCLUSIONS: Theoretical analysis and experimental results both demonstrate that the proposed method outperforms the state-of-the-art methods and is especially effective for the DNA sequence.

Long Non-Coding RNA KCNQ1OT1 Promotes Progression of Hepatocellular Carcinoma by miR-148a-3p/IGF1R Axis.

Accumulating evidence have suggested that long non-coding RNAs (lncRNAs) act as a critical regulator in tumorgenesis. LncRNA KCNQ1OT1 (KCNQ1OT1) has been recently shown to be dysregulated in many cancers. This study was aimed to explore the biological role of KCNQ1OT1 in hepatocellular carcinoma (HCC). In our study, we first observed the expression level of KCNQ1OT1 was distinctly up-regulated in HCC tissues and cell lines compared with adjacent non-cancer tissues and normal liver cell line. And clinical results indicated that higher expression of KCNQ1OT1 was correlated with poor prognosis of patients with HCC. Next, functional studies revealed that knockdown of KCNQ1OT1 induced apoptosis and repressed proliferation, migration and invasion of HCC cells. In addition, knockdown of KCNQ1OT1 suppressed xenograft tumor growth in vivo. Mechanically, we found that KCNQ1OT1 can promote the expression of IGF1R by functioning as a competing endogenous RNA of miR-148a-3p. In conclusion, our results shown the oncogenic role of KCNQ1OT1 in HCC by regulating the miR-148a-3p/IGF1R axis and may provide a new insight and a potential therapeutic target for HCC.

LncRNA MIR194-2HG Promotes Cell Proliferation and Metastasis via Regulation of miR-1207-5p/TCF19/Wnt/ß-Catenin Signaling in Liver Cancer.

PURPOSE: LncRNAs play an important role in tumorigenesis and cancer progression in liver cancer. Although many lncRNAs have been reported, the role of MIR194-2HG and the underlying mechanism mediated by it are still largely unknown in HCC. This study aimed to investigate the biological role and mechanism of MIR194-2HG in liver cancer. MATERIALS AND METHODS: The expression of MIR194-2HG was determined in liver cancer tissues and cells by RT-qPCR. The overall survival rate of MIR194-2HG was analyzed by Kaplan-Meier survival analysis. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and Transwell assays were carried out to detect cell migration and invasion. Western blotting was used to quantify the levels of all proteins. The regulatory mechanism of the MIR194-2HG/miR-1207-5p/TCF19 axis in liver cancer was investigated by dual-luciferase activity reporter assay, Kaplan-Meier survival analysis, and Western blotting. RESULTS: MIR194-2HG was upregulated in liver cancer tissues and cell lines. Liver cancer patients with higher expression of MIR194-2HG revealed poor overall survival compared with those who had lower expression of MIR194-2HG. MIR194-2HG promoted the proliferation, migration, and invasion of HepG2 and Huh7 cells by acting as a ceRNA mechanism for the miR-1207-5p/TCF19 axis to activate the Wnt/ß-catenin signaling pathway. CONCLUSION: MIR194-2HG acts in an oncogenic role and activates the Wnt/ß-catenin signaling pathway via a miR-1207-5p/TCF19 axis-mediated mechanism, which provides a novel avenue for diagnostic or therapeutic interventions in liver cancer.

Bayesian differential analysis of gene regulatory networks exploiting genetic perturbations.

BACKGROUND: Gene regulatory networks (GRNs) can be inferred from both gene expression data and genetic perturbations. Under different conditions, the gene data of the same gene set may be different from each other, which results in different GRNs. Detecting structural difference between GRNs under different conditions is of great significance for understanding gene functions and biological mechanisms. RESULTS: In this paper, we propose a Bayesian Fused algorithm to jointly infer differential structures of GRNs under two different conditions. The algorithm is developed for GRNs modeled with structural equation models (SEMs), which makes it possible to incorporate genetic perturbations into models to improve the inference accuracy, so we name it BFDSEM. Different from the naive approaches that separately infer pair-wise GRNs and identify the difference from the inferred GRNs, we first re-parameterize the two SEMs to form an integrated model that takes full advantage of the two groups of gene data, and then solve the re-parameterized model by developing a novel Bayesian fused prior following the criterion that separate GRNs and differential GRN are both sparse. CONCLUSIONS: Computer simulations are run on synthetic data to compare BFDSEM to two state-of-the-art joint inference algorithms: FSSEM and ReDNet. The results demonstrate that the performance of BFDSEM is comparable to FSSEM, and is generally better than ReDNet. The BFDSEM algorithm is also applied to a real data set of lung cancer and adjacent normal tissues, the yielded normal GRN and differential GRN are consistent with the reported results in previous literatures. An open-source program implementing BFDSEM is freely available in Additional file 1.

A Multi-Sensor Data Fusion Approach for Atrial Hypertrophy Disease Diagnosis Based on Characterized Support Vector Hyperspheres.

Disease diagnosis can be performed based on fusing the data acquired by multiple medical sensors from patients, and it is a crucial task in sensor-based e-healthcare systems. However, it is a challenging problem that there are few effective diagnosis methods based on sensor data fusion for atrial hypertrophy disease. In this article, we propose a novel multi-sensor data fusion method for atrial hypertrophy diagnosis, namely, characterized support vector hyperspheres (CSVH). Instead of constructing a hyperplane, as a traditional support vector machine does, the proposed method generates "hyperspheres" to collect the discriminative medical information, since a hypersphere is more powerful for data description than a hyperplane. In detail, CSVH constructs two characterized hyperspheres for the classes of patient and healthy subject, respectively. The hypersphere for the patient class is developed in a weighted version so as to take the diversity of patient instances into consideration. The hypersphere for the class of healthy people keeps furthest away from the patient class in order to achieve maximum separation from the patient class. A query is labelled by membership functions defined based on the two hyperspheres. If the query is rejected by the two classes, the angle information of the query to outliers and overlapping-region data is investigated to provide the final decision. The experimental results illustrate that the proposed method achieves the highest diagnosis accuracy among the state-of-the-art methods.