We have identified and validated multiple novel lncRNAs associated with tumorigenesis and histological differentiation in human NSCLC. These lncRNAs could be further exploited for the development of useful biomarkers in diagnosis, prognosis, and treatment of NSCLC.

BackgroundDevelopment of robust and efficient methods for analyzing and interpreting high dimension gene expression profiles continues to be a focus in computational biology. The accumulated experiment evidence supports the assumption that genes express and perform their functions in modular fashions in cells. Therefore, there is an open space for development of the timely and relevant computational algorithms that use robust functional expression profiles towards precise classification of complex human diseases at the modular level.ResultsInspired by the insight that genes act as a module to carry out a highly integrated cellular function, we thus define a low dimension functional expression profile for data reduction. After annotating each individual gene to functional categories defined in a proper gene function classification system such as Gene Ontology applied in this study, we identify those functional categories enriched with differentially expressed genes. For each functional category or functional module, we compute a summary measure (s) for the raw expression values of the annotated genes to capture the overall activity level of the module. In this way, we can treat the gene expressions within a functional module as an integrative data point to replace the multiple values of individual genes. We compare the classification performance of decision trees based on functional expression profiles with the conventional gene expression profiles using four publicly available datasets, which indicates that precise classification of tumour types and improved interpretation can be achieved with the reduced functional expression profiles.ConclusionThis modular approach is demonstrated to be a powerful alternative approach to analyzing high dimension microarray data and is robust to high measurement noise and intrinsic biological variance inherent in microarray data. Furthermore, efficient integration with current biological knowledge has facilitated the interpretation of the underlying molecular mechanisms for complex human diseases at the modular level.

BackgroundFerulic acid (4-hydroxy-3-methoxycinnamic acid, FA) is a hydroxycinnamic acid derived from a rich polyphenolic compound. This study aimed to investigate the effect of ferulic acid (4-hydroxy-3-methoxycinnamic acid; FA) on cell proliferation, invasion, apoptosis, and autophagy in Hela and Caski cervical carcinoma cell lines.MethodsThe cell proliferation of FA in Hela and Caski cells were detected by MTT assay. The cell invasion of FA in Hela and Caski cells were detected by Transwell assay. Subsequently, MMP-9 mRNA expression for cell invasion was detected by RT-PCR. Additionally, cell cycle and apoptosis were assayed using flow cytometry. Expression levels of 7 proteins for both cell cycle and autophagy were measured by Western blot analysis.ResultsAfter treated with FA (2.0 mM) for 48 h, the inhibition rates of FA in Hela and Caski cells were 88.3 and 85.4%, respectively. In addition, FA inhibited cell invasion through reducing MMP-9 mRNA expression. FA induced arrest in G0/G1 phase of the cell cycle in Hela and Caski cells with dose dependent (P < 0.05). Meanwhile, FA induced the cell cycle-related proteins expression such as p53 and p21, and reduced Cyclin D1 and Cyclin E levels. Moreover, FA decreased the autophagy-related proteins such as LC3-II, Beclin1 and Atg12-Atg5 in a dose-dependent manner.ConclusionFA can significantly inhibit cell proliferation and invasion in Hela and Caski cells. It might be acted as an anti-cancer drug through inhibiting the autophagy and inducing cell cycle arrest in human cervical carcinoma cells.

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Background/Aims: Circulating long non coding RNAs (lncRNAs) have emerged recently as major players in tumor biology and may be used for cancer diagnosis, prognosis, and as potential therapeutic targets. We explored circulating lncRNA as a predictor for the tumorigenesis of non-small-cell lung cancer (NSCLC). Methods: In this study, we applied a lncRNA microarray to screen for a potential biomarker for NSCLC, utilizing RT-PCR (ABI 7900HT). A multi-stage validation and risk score formula detection analysis was used. Results: We discovered that three lncRNAs (RP11-397D12.4, AC007403.1, and ERICH1-AS1) were up regulated in NSCLC, compared with cancer-free controls, with the merged area under the curve in the training and validation sets of 0.986 and 0.861. Furthermore, the positive predictive value and negative predictive value of the three merged factors were 0.72 and 0.87. We confirmed stable detection of the three lncRNAs by three cycles of freezing and thawing. Conclusions: RP11-397D12.4, AC007403.1, and ERICH1-AS1 may be potential biomarkers for predicting the tumorigenesis of NSCLC in the future.

Cinobufagin (CBF) is isolated from the skin and posterior auricular glands of the Asiatic toad (Bufo gargarizans). This study investigated the reversal effect of CBF on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in colon cancer. The effect of CBF on the cytotoxicity of anticancer drugs in P-gp overexpressing LoVo/ADR, HCT116/L, Cao-2/ADR cells and their parental cells was determined using CCK-8 assay. Apoptosis of anti-cancer drugs and accumulation of doxorubicin (DOX) and Rhodamine 123 (Rho123) in P-gp overexpressing cells were evaluated by flow cytometry. Results indicated that CBF significantly enhanced the sensitivity of P-gp substrate drugs on P-gp overexpressing cells, but had no effect on their parental cells. CBF enhanced the effect of DOX against P-gp-overexpressing LoVo/ADR cell xenografts in nude mice. Moreover, CBF also increased cell apoptosis of chemotherapy agents and intracellular accumulation of DOX and Rho123 in the MDR cells. Further research on the mechanisms revealed non-competitive inhibition of P-gp ATPase activity, but without altering the expression of P-gp. These findings demonstrated that CBF could be further developed into a safe and potent P-gp modulator for combination use with anticancer drugs in cancer chemotherapy.

BackgroundHesperidin (30, 5, 9-dihydroxy-40-methoxy-7-orutinosyl flavanone) is a flavanone that is found mainly in citrus fruits and has been shown to have some anti-neoplastic effects. The aim of the present study was to investigate the effect of hesperidin on apoptosis in human cervical cancer HeLa cells and to identify the mechanism involved.MethodsCells were treated with hesperidin (0, 20, 40, 60, 80, and 100 μM) for 24, 48, or 72 h and relative cell viability was assessed using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay.ResultsHesperidin inhibited the proliferation of HeLa cells in a concentration- and time-dependent manner. Hesperidin-induced apoptosis in HeLa cells was characterized by increased nuclear condensation and DNA fragmentation. Furthermore, increased levels of GADD153/CHOP and GRP78 indicated hesperidin-induced apoptosis in HeLa cells involved a caspase-dependent pathway, presumably downstream of the endoplasmic reticulum stress pathway. Both of these proteins are hallmarks of endoplasmic reticulum stress. Hesperidin also promoted the formation of reactive oxygen species, mobilization of intracellular Ca2+, loss of mitochondrial membrane potential (ΔΨm), increased release of cytochrome c and apoptosis-inducing factor from mitochondria, and promoted capase-3 activation. It also arrested HeLa cells in the G0/G1 phase in the cell cycle by downregulating the expression of cyclinD1, cyclinE1, and cyclin-dependent kinase 2 at the protein level. The effect of hesperidin was also verified on the human colon cancer cell HT-29 cells.ConclusionWe concluded that hesperidin inhibited HeLa cell proliferation through apoptosis involving endoplasmic reticulum stress pathways and cell cycle arrest.