Long noncoding RNAs as tumorigenic factors and therapeutic targets for renal cell carcinoma.

Approximately 338,000 patients are diagnosed with kidney cancer worldwide each year, and renal cell carcinoma (RCC), which is derived from renal epithelium, accounts for more than ninety percent of the malignancy. Next generation RNA sequencing has enabled the identification of novel long noncoding RNAs (lncRNAs) in the past 10 years. Recent studies have provided extensive evidence that lncRNAs bind to chromatin modification proteins, transcription factors, RNA-binding proteins and microRNAs, and thereby modulate gene expression through regulating chromatin status, gene transcription, pre-mRNA splicing, mRNA decay and stability, protein translation and stability. In vitro and in vivo studies have demonstrated that over-expression of oncogenic lncRNAs and silencing of tumor suppressive lncRNAs are a common feature of human RCC, and that aberrant lncRNA expression is a marker for poor patient prognosis, and is essential for the initiation and progression of RCC. Because lncRNAs, compared with mRNAs, are expressed in a tissue-specific manner, aberrantly expressed lncRNAs can be better targeted for the treatment of RCC through screening small molecule compounds which block the interaction between lncRNAs and their binding proteins or microRNAs.

Plasma Long Non-Coding RNA RP11-438N5.3 as a Novel Biomarker for Non-Small Cell Lung Cancer.

BACKGROUND: Lung cancer is one of the most common malignancies around the world. The lack of early diagnosis and effective treatment strategies contributes to the poor prognosis of patients with lung cancer. Recent studies have implied the role of long non-coding RNAs (lncRNAs) in oncogenesis. The purpose of our study was to identify specific lncRNAs which were correlated with non-small cell lung cancer (NSCLC) and their potential functions. MATERIALS AND METHODS: The global plasma lncRNA profiling was performed using LncPathTM Human Cancer Array, and 11 lncRNAs were then selected for quantitative reverse transcription PCR (qRT-PCR) validation in 138 plasma samples from 69 NSCLC patients and 69 healthy controls (HCs). A noteworthy lncRNA, RP11-438N5.3, the function of which was previously unknown, was further explored on the aspect of the correlation of its expression level with clinicopathological factors. RESULTS: The results revealed that plasma level of RP11-438N5.3 was significantly lower in NSCLCs than that in HCs (p <0.01). Receiver operating characteristic (ROC) analyses showed that the area under the ROC curve (AUC) for plasma RP11-438N5.3 was 0.814 (95% CI, 0.743-0.885; p<0.01). High expression of RP11-438N5.3 in plasma correlated with favorable prognosis for NSCLC patients (Hazard ratio = 2.827; 95% CI: 1.036 to 7.718; p = 0.024; Cox regression analysis). Moreover, we found that the plasma level of stromal interaction molecule 1 (STIM1) mRNA was remarkably higher in NSCLC compared with HC (p<0.01), and the AUC for STIM1 was 0.753 (95% CI, 0.673-0.833; p<0.01), RP11-438N5.3 and STIM1 were inversely correlated with each other. CONCLUSION: Our results indicated that RP11-438N5.3 and STIM1 might provide a new strategy for NSCLC diagnosis. Furthermore, increased circulating RP11-438N5.3 level holds great potential in indicating a beneficial prognosis in NSCLC patients.

Entropy SVM-Based Recognition of Transient Surges in HVDC Transmissions.

Protection based on transient information is the primary protection of high voltage direct current (HVDC) transmission systems. As a major part of protection function, accurate identification of transient surges is quite crucial to ensure the performance and accuracy of protection algorithms. Recognition of transient surges in an HVDC system faces two challenges: signal distortion and small number of samples. Entropy, which is stable in representing frequency distribution features, and support vector machine (SVM), which is good at dealing with samples with limited numbers, are adopted and combined in this paper to solve the transient recognition problems. Three commonly detected transient surges-single-pole-to-ground fault (GF), lightning fault (LF), and lightning disturbance (LD)-are simulated in various scenarios and recognized with the proposed method. The proposed method is proved to be effective in both feature extraction and type classification and shows great potential in protection applications.

Rad51 in regulating the radiosensitivity of non-small cell lung cancer with different epidermal growth factor receptor mutation status.

BACKGROUND: Non-small cell lung cancer (NSCLC) harboring kinase-domain mutations in epidermal growth factor receptors (EGFR) has been observed to be sensitive to ionizing radiation (IR). We explore Rad51-dependent homologous recombination (HR) DNA repair in regulating radiosensitivity in two NSCLC cell lines with different EGFR mutation status. METHODS: NSCLC cell lines, wild-type EGFR A549 and mutant EGFR H820 with an in-frame deletion in exon 19 of EGFR (ΔE746-E750), were cultured. Radiosensitivity was estimated by colony forming assay. Rad51 expression was evaluated by quantitative real time-polymerase chain reaction and Western-blot. Lentiviral small hairpin ribonucleic acid-Rad51 and ΔE746-E750 deletion mutant EGFR were constructed and transfected into cells. Flowcytometry assay was used to analyze DNA double strand breaks, cell cycle alterations, and apoptosis. RESULTS: A549 had a higher survival factor (SF)2 (0.66 vs. 0.44) and lower α/ß value (4.07 vs. 9.01). Compared with the A549 cell, the H820 cell exhibited defective arrest in the S-phase, a higher rate of G2/M accumulation, early apoptosis, and residual γ-H2AX. Downregulated Rad51 expression decreased SF2 (0.42 vs. 0.31) and increased the α/ß ratio (7.51 vs. 10.5), G2/M accumulation, early apoptosis, and γ-H2AX in two cell lines. H820 had a low IR-induced Rad51 expression and nuclear translocation. Exogenous expression of the ΔE746-E750 deletion mutant EGFR caused the A549 cell to become more radiosensitive. CONCLUSIONS: An EGFR mutated NSCLC cell line is sensitive to IR , which is correlated with reduced IR-induced Rad51 expression and nuclear translocation. The signaling pathway of EGFR maintaining Rad51 protein levels maybe a novel lung cancer therapeutic target to overcome radioresistance.

Synchronous primary cancers of trachea and esophagus and ventricular tachycardia.

The incidence of multiple primary cancers involving trachea is rare. We present a case of synchronous double primary cancer of trachea and esophagus in a 70-year-old woman, with a special symptom of ventricular tachycardia and no history of smoking and alcohol drinking. Biopsies from multiple foci demonstrated the patient had primary small cell cancer of trachea and squamous cell carcinoma in situ of esophagus. The patient was successfully treated with four cycles of chemotherapy consisting of etoposide and carboplatin (EC) followed by thoracic radiotherapy (60 Gy in 30 fractions, in 6 weeks), and was evaluated to have complete response of tumor. To our knowledge, there is no synchronous cancer of trachea and esophagus has been reported in English literature, and our experience showed sequential EC chemotherapy and radiotherapy provided an effective treatment to control both cancers.