BackgroundDeregulations of long non-coding RNAs (lncRNAs) have been implicated in cancer initiation and progression. Current methods can only capture differential expression of lncRNAs at the population level and ignore the heterogeneous expression of lncRNAs in individual patients.MethodsWe propose a method (LncRIndiv) to identify differentially expressed (DE) lncRNAs in individual cancer patients by exploiting the disrupted ordering of expression levels of lncRNAs in each disease sample in comparison with stable normal ordering. LncRIndiv was applied to lncRNA expression profiles of lung adenocarcinoma (LUAD). Based on the expression profile of LUAD individual-level DE lncRNAs, we used a forward selection procedure to identify prognostic signature for stage I-II LUAD patients without adjuvant therapy.ResultsIn both simulated data and real pair-wise cancer and normal sample data, LncRIndiv method showed good performance. Based on the individual-level DE lncRNAs, we developed a robust prognostic signature consisting of two lncRNA (C1orf132 and TMPO-AS1) for stage I-II LUAD patients without adjuvant therapy (P = 3.06 × 10−6, log-rank test), which was confirmed in two independent datasets of GSE50081 (P = 1.82 × 10−2, log-rank test) and GSE31210 (P = 7.43 × 10−4, log-rank test) after adjusting other clinical factors such as smoking status and stages. Pathway analysis showed that TMPO-AS1 and C1orf132 could affect the prognosis of LUAD patients through regulating cell cycle and cell adhesion.Conclusions LncRIndiv can successfully detect DE lncRNAs in individuals and be applied to identify prognostic signature for LUAD patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0666-z) contains supplementary material, which is available to authorized users.

The adjuvant chemotherapy, such as cisplatin, doxorubicin, and methotrexate has significantly improved survival of osteosarcoma patients. However, the chemoresistance which arose with the chemotherapy blocks achieving favorable outcomes for some patients and finally led to relapse or metastatic disease. Studies have shown paradoxical functions of autophagy in tumor development, which has been demonstrated by microRNAs. In the present study, we determined the involvement of autophagy during the chemotherapy of osteosarcoma cell line, U-2 OS, and further determined the regulation of miR-101 on the autophagy in the U-2 OS cells. Results demonstrated that doxorubicin treatment of U-2 OS cells induced significantly high level of autophagy-characteristic acidic vesicular organelles (AVOs), and induced significant autophagy related protein expression in U-2 OS cells. While the miR-101 could significantly reduce the doxorubicin-induced AVOs and block the autophagy related protein expression in U-2 OS cells. Moreover, the autophagy blockage by miR-101 sensitized the U-2 OS cells to doxorubicin treatment. In summary, miR-101 blocks autophagy during the chemotherapy in osteosarcoma cells and enhances chemosensitivity in vitro.

Abstract. Oxidative stress is considered to be an important cause of dysfunction in chondrocytes and articular cartilage degradation, which leads to the pathogenesis of osteoarthritis (OA) and cartilage aging. The present study aimed to assess the effects of the widely applied antioxidant, ascorbic acid (AA), on human chondrocytes against hydrogen peroxide (H 2 O 2 ) in vitro. Using annexin V-fluorescein isothiocyanate, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and senescence-associated β-galactosidase assays, the present study identified that AA reduced apoptosis, reduced the loss of viability and markedly decreased H 2 O 2 -mediated senescence in cells treated with H 2 O 2 . Furthermore, AA not only stimulated the expression levels of collagens and proteoglycans, but also inhibited the differentiation of chondrocytes under conditions of oxidative stress. In addition, reverse transcription-quantitative polymerase chain reaction and western blotting demonstrated that AA decreased the activity of nrf2, NF-κB, AP1 and matrix metalloproteinase-3, which is stimulated by H 2 O 2 . In conclusion, AA efficiently protected human chondrocytes against damage induced by H 2 O 2 by regulating multiple regulatory pathways.

The irreproducibility problem seriously hinders the studies on transcriptional signatures for predicting relapse risk of early stage colorectal cancer (CRC) patients. Through reviewing recently published 34 literatures for the development of CRC prognostic signatures based on gene expression profiles, we revealed a surprising phenomenon that 33 of these studies analyzed CRC samples with and without adjuvant chemotherapy together in the training and/or validation datasets. This data misuse problem could be partially attributed to the unclear and incomplete data annotation in public data sources. Furthermore, all the signatures proposed by these studies were based on risk scores summarized from gene expression levels, which are sensitive to experimental batch effects and risk compositions of the samples analyzed together. To avoid the above-mentioned problems, we carefully selected three qualified large datasets to develop and validate a signature consisting of three pairs of genes. The within-sample relative expression orderings of these gene pairs could robustly predict relapse risk of stage II CRC samples assessed in different laboratories. The transcriptional and functional analyses provided clear evidence that the high risk patients predicted by the proposed signature represent patients with micro-metastases.