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101.
Boxin Zhang Haihui Wang Ziyan Guo Xinhai Zhang 《Journal of cellular physiology》2019,234(10):18781-18791
Recent evidence suggests that long noncoding RNAs (lncRNAs) are essential regulators of many cancer-related processes, including cancer cell proliferation, invasion, and migration. There is thus a reason to believe that the detection of lncRNAs may be useful as a diagnostic and prognostic strategy for cancer detection, however, at present no effective genome-wide tests are available for clinical use, constraining the use of such a strategy. In this study, we performed a comprehensive assessment of lncRNAs expressed in samples in the head and neck squamous cell carcinoma (HNSCC) cohort available in The Cancer Genome Atlas database. A risk score (RS) model was constructed based on the expression data of these 15 lncRNAs in the validation data set of HNSCC patients and was subsequently validated in validation data set and the entire data set. We were able to stratify patients into high- and low-risk categories, using our lncRNA expression panel to determine an RS, with significant differences in overall survival (OS) between these two groups in our test set (median survival, 1.863 vs. 5.484 years; log-rank test, p < 0.001). We were able to confirm the predictive value of our 15-lncRNA signature using both a validation data set and a full data set, finding our signature to be reproducible and effective as a means of predicting HNSCC patient OS. Through the multivariate Cox regression and stratified analyses, we were further able to confirm that the predictive value of this RS was independent of other predictive factors such as clinicopathological parameters. The Gene set enrichment analysis revealed potential functional roles for these 15 lncRNAs in tumor progression. Our findings indicate that an RS established based on a panel of lncRNA expression signatures can effectively predict OS and facilitate patient stratification in HNSCC. 相似文献
102.
Liang Yi Lei Ouyang Shuang Wang Shi-Sheng Li Xin-Ming Yang 《Journal of cellular physiology》2019,234(10):19088-19102
Protein regulator of cytokinesis 1 (PRC1) has been reported in correlation with various malignancies. Functionality of PRC1 in nasopharyngeal carcinoma (NPC) was investigated, in perspective of long noncoding RNA (lncRNA) regulatory circuitry. Aberrant expressed messenger RNA and lncRNA were screened out from the Gene Expression Omnibus microarray database. NPC cell line CNE-2 was adopted for in vitro study and transfected with mimic or short hairpin RNA of miR-194-3p and PTPRG-AS1. The radioactive sensitivity, cell viability, migration, invasion, and apoptosis were detected. PTPRG-AS1 and PRC1 were upregulated in NPC, whereas miR-194-3p was downregulated. PTPRG-AS1 was found to specifically bind to miR-194-3p as a competing endogenous RNA and miR-194-3p targets and negatively regulates PRC1. Overexpressed miR-194-3p or silenced PTPRG-AS1 resulted in enhanced sensitivity to radiotherapy and cell apoptosis along with suppressed cell migration, invasion and proliferation in NPC. Furthermore, impaired tumor formation was also caused by miR-194-3p overexpression or PTPRG-AS1 suppression through xenograft tumor in nude mice. In our study, PTPRG-AS1/miR-194-3p/PRC1 regulatory circuitry was revealed in NPC, the mechanism of which can be of clinical significance for treatment of NPC. 相似文献
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Pranjal Kumar Seema Khadirnaikar Sudhanshu Kumar Shukla 《Journal of cellular physiology》2019,234(9):16021-16031
The prognostic signatures play an essential role in the era of personalised therapy for cancer patients including lung adenocarcinoma (LUAD). Long noncoding RNA (LncRNA), a relatively novel class of RNA, has shown to play a crucial role in all the areas of cancer biology. Here, we developed and validated a robust LncRNA-based prognostic signature for LUAD patients using three different cohorts. In the discovery cohort, four LncRNAs were identified with 10% false discovery rate and a hazard ratio of >10 using univariate Cox regression analysis. A risk score, generated from the four LncRNAs’ expression, was found to be a significant predictor of survival in the discovery and validation cohort (p = 9.97 × 10 −8 and 1.41 × 10 −3, respectively). Further optimisation of four LncRNAs signature in the validation cohort, generated a three LncRNAs prognostic score (LPS), which was found to be an independent predictor of survival in both the cohorts ( p = 1.00 × 10 −6 and 7.27 × 10 −4, respectively). The LPS also significantly divided survival in clinically important subsets, including Stage I ( p = 9.00 × 10 −4 and 4.40 × 10 −2, respectively), KRAS wild-type (WT), KRAS mutant ( p = 4.00 × 10 −3 and 4.30 × 10 −2, respectively) and EGFR WT ( p = 2.00 × 10 −4). In multivariate analysis LPS outperformed, eight previous prognosticators. Further, individual members of LPS showed a significant correlation with survival in microarray data sets. Mutation analysis showed that high-LPS patients have a higher mutation rate and inactivation of the TP53 pathway. In summary, we identified and validated a novel LncRNA signature LPS for LUAD. 相似文献
105.
Richard Wetherbee Vanessa Rossetto Marcelino Joana F. Costa Brenna Grant Simon Crawford Ross F. Waller Robert A. Andersen Drew Berry Geoffrey I. McFadden Heroen Verbruggen 《Journal of phycology》2019,55(6):1210-1225
Prasinophytes (Chlorophyta) are a diverse, paraphyletic group of planktonic microalgae for which benthic species are largely unknown. Here, we report a sand‐dwelling, marine prasinophyte with several novel features observed in clonal cultures established from numerous locations around Australia. The new genus and species, which we name Microrhizoidea pickettheapsiorum (Mamiellophyceae), alternates between a benthic palmelloid colony, where cell division occurs, and a planktonic flagellate. Flagellates are short lived, settle and quickly resorb their flagella, the basal bodies then nucleate novel tubular appendages, termed “microrhizoids”, that lack an axoneme and function to anchor benthic cells to the substratum. To our knowledge, microrhizoids have not been observed in any other green alga or protist, are slightly smaller in diameter than flagella, generally contain nine microtubules, are long (3–5 times the length of flagella) and are not encased in scales. Following settlement, cell divisions result in a loose, palmelloid colony, each cell connected to the substratum by two microrhizoids. Flagellates are round to bean‐shaped with two long, slightly uneven flagella. Both benthic cells and flagellates, along with their flagella, are encased in thin scales. Phylogenies based on the complete chloroplast genome of Microrhizoidea show that it is clearly a member of the Mamiellophyceae, most closely related to Dolichomastix tenuilepsis. More taxon‐rich phylogenetic analyses of the 18S rRNA gene, including metabarcodes from the Tara Oceans and Ocean Sampling Day projects, confidently show the distinctive nature of Microrhizoidea, and that the described biodiversity of the Mamiellophyceae is a fraction of its real biodiversity. The discovery of a largely benthic prasinophyte changes our perspective on this group of algae and, along with the observation of other potential benthic lineages in environmental sequences, illustrates that benthic habitats can be a rich ground for algal biodiscovery. 相似文献
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Malignant glioma is a severe type of brain tumor with a grim prognosis. The occurrence of resistance compromises the efficacy of chemotherapy for glioma. Long noncoding RNA growth arrest-specific 5 (GAS5) has recently become an attractive target for cancer therapy by regulating cell growth, invasion, and migration. Nevertheless, its role in glioma chemoresistance remains elusive. In the current study, the expression of GAS5 was decreased in glioma cell lines, and lower levels of GAS5 were observed in U138 and LN18 glioma cells that had low sensitivity to cisplatin. Functional assay confirmed that knockdown of GAS5 enhanced cell resistance to cisplatin in U87 cells, which had a relatively high expression of GAS5. Conversely, elevation of GAS5 increased cell sensitivity to cisplatin in U138 cells that had a relatively low expression of GAS5. Mechanistically, cisplatin exposure evoked excessive autophagy concomitant with an increase in autophagy-related LC3II expression and a decrease in autophagy substrate p62 expression, which was reversely muted after GAS5 overexpression. In addition, GAS5 restored cisplatin-inhibited mammalian target of rapamycin (mTOR) activation. Preconditioning with mTOR antagonist rapamycin engendered not only mTOR inhibition but also abrogated GAS5-mediated depression in cisplatin-evoked autophagy. Notably, blocking the mTOR pathway also attenuated GAS5-increased sensitivity to cisplatin in U138 cells. Cumulatively, these findings indicate that GAS5 may blunt the resistance of glioma cells to cisplatin by suppressing excessive autophagy through the activation of mTOR signaling, implying a promising therapeutic strategy against chemoresistance in glioma. 相似文献