BackgroundOxaliplatin resistance is a major challenge for treatment of advanced colorectal cancer (CRC). Both acquisition of epithelial-mesenchymal transition (EMT) and suppressed drug accumulation in cancer cells contributes to development of oxaliplatin resistance. Aberrant expression of small noncoding RNA, miR-128-3p, has been shown to be a key regulator in tumorigenesis and cancer development. However, its roles in the progression of CRC and oxaliplatin-resistance are largely unknown.MethodsOxaliplatin-resistant CRC and normal intestinal FHC cells were transfected with a miR-128-3p expression lentivirus. After transfection, FHC-derived exosomes were isolated and co-cultured with CRC cells. miR-128-3p expression in resistant CRC cells, FHC cells, and exosomes was quantified by quantitative real-time PCR (RT-qPCR). The mRNA and protein levels of miR-128-3p target genes in resistant CRC cells were quantified by RT-qPCR and western blot, respectively. The effects of miR-128-3p on CRC cell viability, apoptosis, EMT, motility and drug efflux were evaluated by CCK8, flow cytometry, Transwell and wound healing assays, immunofluorescence, and atomic absorption spectrophotometry. Xenograft models were used to determine whether miR-128-3p loaded exosomes can re-sensitize CRC cells to oxaliplatin in vivo.ResultsIn our established stable oxaliplatin-resistant CRC cell lines, in vitro and vivo studies revealed miR-128-3p suppressed EMT and increased intracellular oxaliplatin accumulation. Importantly, our results indicated that lower miR-128-3p expression was associated with poor oxaliplatin response in advanced human CRC patients. Moreover, data showed that miR-128-3p-transfected FHC cells effectively packaged miR-128-3p into secreted exosomes and mediated miR-128-3p delivery to oxaliplatin-resistant cells, improving oxaliplatin response in CRC cells both in vitro and in vivo. In addition, miR-128-3p overexpression up-regulated E-cadherin levels and inhibited oxaliplatin-induced EMT by suppressing Bmi1 expression in resistant cells. Meanwhile, it also decreased oxaliplatin efflux through suppressed expression of the drug transporter MRP5.ConclusionOur results demonstrate that miR-128-3p delivery via exosomes represents a novel strategy enhancing chemosensitivity in CRC through negative regulation of Bmi1 and MRP5. Moreover, miR-128-3p may be a promising diagnostic and prognostic marker for oxaliplatin-based chemotherapy.Electronic supplementary materialThe online version of this article (10.1186/s12943-019-0981-7) contains supplementary material, which is available to authorized users.

To study the effect of water on the properties of choline chloride (ChCl)/urea mixtures (1:2 on a molar basis), the density and viscosity of ChCl/ urea (1:2) with water were measured at temperatures from 298.15 K to 333.15 K at atmospheric pressure, the CO 2 solubility in ChCl/urea (1:2) with water was determined at 308.2 K, 318.2 K, and 328.2 K and at pressures up to 4.5 MPa. The results show that the addition of water significantly decreases the viscosity of ChCl/urea (1:2), whereas the effects on their density and CO 2 solubility are much weaker. The CO 2 solubility in ChCl/urea (1:2) with water was represented with the Nonrandom-Two-Liquid Redlich−Kwong (NRTL-RK) model. The excess molar volume and excess molar activation energy were further determined. The CO 2 absorption enthalpy was calculated and dominated by the CO 2 dissolution enthalpy, and the magnitude of the CO 2 dissolution enthalpy decreases with the increase of water content.

Lung cancer is the first leading cause of cancer deaths worldwide. Non‐small cell lung cancer (NSCLC) is the most common type of lung cancer. Increasing evidence shows that long noncoding RNA (lncRNA) are capable of modulating tumor initiation, proliferation and metastasis. In the present study, we aimed to evaluate whether circulating lncRNA could be used as biomarkers for diagnosis and prognosis of NSCLC. Expression profiles of 14 lncRNA selected from other studies were validated in 20 pairs of tissues by quantitative real‐time PCR, and the dysregulated lncRNA thus identified were further validated in serum samples from two independent cohorts along with three tumor makers (CEA, CYFRA21‐1, and SCCA). Receiver‐operating characteristic analysis was utilized to estimate the diagnostic efficiency of the candidate lncRNA and tumor markers. Importantly, we observed an association between lncRNA expression and overall survival (OS) rate of NSCLC. The expressions of SOX2 overlapping transcript (SOX2OT) and ANRIL were obviously upregulated in NSCLC tissues and serum samples compared with normal controls (P < 0.01). Based on the data from the training set, we next used a logistic regression model to construct an NSCLC diagnostic panel consisting of two lncRNA and three tumor markers. The area under the curve of this panel was 0.853 (95% confidence interval = 0.804–0.894, sensitivity = 77.1%, specificity = 79.2%), and this was distinctly superior to any biomarker alone (all at P < 0.05). Similar results were observed in the validation set. Intriguingly, Kaplan–Meier analysis demonstrated that low expressions of SOX2OT and ANRIL were both associated with higher OS rate (P = 0.008 and 0.017, respectively), and SOX2OT could be used as an independent prognostic factor (P = 0.036). Taken together, our study demonstrated that the newly developed diagnostic panel consisting of SOX2OT, ANRIL, CEA, CYFRA21‐1, and SCCA could be valuable in NSCLC diagnosis. LncRNA SOX2OT and ANRIL might be ideal biomarkers for NSCLC prognosis.

35 novel DESs are synthesized and screened in terms of their CO2 solubility and viscosity.

Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and progression. We aimed to identify a panel of lncRNAs for the diagnosis and recurrence prediction in bladder cancer (BC). The expression of 13 candidate lncRNAs was investigated in 80 BC and matched adjacent normal tissues via quantitative real-time PCR. The differentially expressed lncRNAs were then analyzed in 240 serum samples (training set) and three lncRNAs (MEG3, SNHG16 and MALAT1) showed differential expression. A logistic regression model was constructed using the training set and validated in an independent cohort of 200 serum samples (validation set). The AUC of the three-lncRNA panel was 0.865 for the training and 0.828 for the validation set. The diagnostic performance of the lncRNA panel for Ta, T1, and T2–T4 were 0.778, 0.805, and 0.880, which were significantly higher than those of urine cytology (0.548, 0.604, and 0.682, respectively). Moreover, we determined that low expression of MEG3 was associated with poor recurrence-free survival by Kaplan-Meier analysis (p = 0.028), univariate Cox analysis (p = 0.033) and multivariate Cox analysis (p = 0.046). In conclusion, our results identified a three-lncRNA panel for BC diagnosis and a recurrence-independent prognostic factor, MEG3.

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Our study established a distinctive 4-lncRNA panel with considerable diagnostic value and identified NR_029373 and NR_034119 as potential biomarkers for CRC prognosis prediction.

Cell‐free long non‐coding RNAs (lncRNAs) are stably present in urine and can serve as non‐invasive biomarkers for cancer. We aimed to identify signatures of lncRNAs in urine for diagnosis and prognosis of bladder cancer (BC). Screening of lncRNAs by microarray analysis was performed using urine samples of 10 BC patients and 10 controls. Expressions of candidate lncRNAs were evaluated in the training and validation set including 230 BC patients and 230 controls by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). A two‐lncRNA panel (uc004cox.4 and GAS5) was constructed and provided high diagnostic accuracy of BC with an area under the curve (AUC) of 0.885 (95% CI, 0.836‐0.924). The AUCs of the lncRNA panel for Ta, T1 and T2‐T4 were 0.843, 0.867 and 0.923, respectively, significantly higher than those of urine cytology (all P < .05). Kaplan‐Meier analysis revealed that higher level of uc004cox.4 was associated with poor recurrence‐free survival (RFS) of non‐muscle invasive BC (NMIBC) (P = .008). Additionally, Cox regression analysis indicated that uc004cox.4 was an independent prognostic factor for RFS of NMIBC (P = .018). Taken together, our findings indicated that urinary lncRNA signatures possessed potential clinical value for BC diagnosis. Moreover, uc004cox.4 could provide prognostic information for NMIBC.