Circular RNA expression pattern in cisplatin-resistant osteosarcoma cells.

BACKGROUND: Cisplatin resistance associated with circular RNA (circRNA) in osteosarcoma (OS) is not fully understood. The present study aimed to reveal the expression profile of circRNAs related to cisplatin resistance in OS. METHODS: Cisplatin-resistant OS cell lines (U2OS-R and MG63-R) were induced using different concentrations of cisplatin and RNA sequencing (RNA-seq) was performed to screen differentially expressed circRNAs in these cells. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the function of the differentially expressed circRNAs. The circRNAs identified by RNA-seq were randomly selected for expression identification by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: A total of 343 circRNAs were differentially expressed in U2OS-R cells compared with U2OS cells. Among these circRNAs, 253 were upregulated and 90 were downregulated. Analysis of the characteristics of the differentially expressed circRNAs showed that upregulated circRNAs were mainly distributed in chromosomes 1, 2, 3, 7, and 8, while downregulated circRNAs were distributed in all chromosomes except the X chromosome. GO and KEGG analyses revealed that the differentially expressed circRNAs were enriched in metabolic pathways, pathways in cancer, adherens junction, proteoglycans in cancer, and transcriptional misregulation in cancer pathway. Furthermore, three circRNAs (hsa_circ_0008336, hsa_circ_0004664, and hsa_circ_0003302) were upregulated in both U2OS-R and MG63-R cells. CONCLUSIONS: Cisplatin-resistant cell lines showed a distinct circRNA expression profile. In particular, hsa_circ_0008336, hsa_circ_0004664, and hsa_circ_0003302 were upregulated in cisplatin-resistant cells and may be involved in the pathology of cisplatin resistance in OS.

The lncRNA MIR4435-2HG is upregulated in hepatocellular carcinoma and promotes cancer cell proliferation by upregulating miRNA-487a.

BACKGROUND: Given the high mortality rate and unclear pathogenesis for liver cancer, investigation of its molecular mechanisms is essential. We focused on the long non-coding RNA (lncRNA) MIR4435-2HG, which was recently reported to be oncogenic in lung cancer and the microRNA miRNA-487a, which has been reported to be oncogenic in hepatocellular carcinoma (HCC). Our aim was to determine if the former has a role in HCC, and to further validate the role of the latter. METHODS: Samples from 64 patients with HCC were taken at The Third Affiliated Hospital of Sun Yat-Sen University. Cell transfection and PCR were applied. RESULTS: We found that MIR4435-2HG and miRNA-487a were upregulated in tumor tissues compared to adjacent healthy tissues from HCC patients. The expression of MIR4435-2HG was significantly affected by tumor size but not by tumor metastasis. Correlation analysis showed that MIR4435-2HG and miRNA-487a were positively correlated in both the tumor tissues and adjacent healthy tissues from HCC patients. Overexpression of MIR4435-2HG led to upregulation of miRNA-487a in the cells of HCC cell lines, while overexpression of miRNA-487a did not significantly affect MIR4435-2HG. Overexpression of MIR4435-2HG and miRNA-487a promoted the proliferation of cells of HCC cell lines, and miRNA-487a knockdown partially attenuated the enhancing effects of MIR4435-2HG overexpression on cancer cell proliferation. CONCLUSION: MIR4435-2HG is upregulated in HCC and promotes cancer cell proliferation possibly by upregulating miRNA-487a.

miR-431-5p alters the epithelial-to-mesenchymal transition markers by targeting UROC28 in hepatoma cells.

OBJECTIVE: MicroRNA (miR)-431 plays an essential role in various human cancer types, particularly in the process of invasion. However, the function and mechanism of miR-431-5p in the invasion of hepatocellular carcinoma (HCC) remain undefined. METHODS: The expression levels of miR-431-5p and its potential target protein UROC28 in hepatocellular carcinoma cells and tissues were detected, and the levels of EMT markers in vivo and in vitro were also detected. RESULTS: MiR-431-5p was downregulated in HCC cell lines and tissues and associated with vascular invasion and tumor encapsulation. Furthermore, miR-431-5p was able to influence the epithelialto-mesenchymal transition (EMT) process in HCCLM3 and HUH7 cells. Mechanistically, it was discovered that miR-431-5p repressed invasion by targeting UROC28. Furthermore, miR-431-5p influenced the EMT markers in HCCLM3 and HUH7 cells by downregulating UROC28 expression. Similarly, in vivo assays confirmed that miR-431-5p upregulation in HCC cells remarkably inhibited tumor proliferation and influenced the EMT markers. CONCLUSION: The current study has demonstrated that the miR-431-5p/UROC28 axis acts possible influence on the EMT in HCC. Upregulation of miR-431-5p could be an original approach for inhibiting tumor invasion.

Circular RNAs are differentially expressed in liver ischemia/reperfusion injury model.

Liver ischemia/reperfusion (I/R) injury has high mortality due to the intense inflammatory process occurs in the liver. However, the pathological mechanism underlying I/R injury is still not clear. Recent works showed that circular RNAs play critical roles in many human diseases. In this study, the occurrence of liver I/R injury was validated by an analysis of the blood samples and hematoxylin-eosin (HE) staining of liver tissues. Total RNA was purified and followed by RNA-seq in the purpose of screening the circRNAs in significant differentially expression, which were validated by quantitative PCR. GO and KEGG analysis were performed to determine the function of these differentially expressed circular RNAs. The circular structure of the circRNA was validated with gel electrophoresis and RNase R treatment. We found that some circular RNAs were differentially expressed in Liver I/R mouse models through bioinformatics analysis. These circular RNAs play roles in biological process, cellular component, and molecular function through GO analysis. Meanwhile, Hippo signaling pathway was found to be correlated with circular RNAs function in I/R models by KEGG analysis. To further validate bioinformatics data, two up-regulated and three down-regulated circular RNAs were confirmed in I/R models. The circularity of these differentially expressed circular RNAs was validated through gel electrophoresis and RNase R treatment. In summary, this work provides new insights into the mechanism underlying pathogenesis of liver I/R injury, providing new and potentially efficient targets against I/R injury.

The expression status of ZIC2 as a prognostic marker for nasopharyngeal carcinoma.

Zinc finger protein ZIC2 is a transcription factor encoded by the ZIC2 gene, which can interact with various DNAs and proteins. ZIC2 expression may promote cell proliferation and inhibit apoptosis. Recent studies have reported that ZIC2 acts as an oncogene in various cancers. The expression and distinct prognostic value of ZIC2 in NPC is not well established. The aim of this study was to investigate ZIC2 expression and its prognostic significance in nasopharyngeal carcinoma (NPC). The ZIC2 expressions at the mRNA levels in NPC tissues and normal tissues were investigated using Oncomine analysis. ZIC2 protein expression was analyzed in paraffin-embedded NPC tissues by immunohistochemistry. Statistical analyses were performed to evaluate the clinicopathological significance of ZIC2 expression. The result shows the expression of ZIC2 mRNA is significantly elevated in NPC tissue compared with normal nasopharynx tissues. In paraffin-embedded tissue samples, the immunoreactivity of ZIC2 was primarily seen in the nuclei and cytoplasms within tumor cells. High ZIC2 expression was obviously related to poor OS and DFS compared to low ZIC2 expression. In a multivariate analysis, the expression of ZIC2 was an independent prognostic factor for OS and DFS. ZIC2 is up-regulated in NPC and associated with histology and survival. ZIC2 may serve as a prognostic indicator for patients with NPC.

LncRNA XIST functions as a molecular sponge of miR-194-5p to regulate MAPK1 expression in hepatocellular carcinoma cell.

Increasing evidence highlights the important role of XIST, a long non-coding RNA (lncRNA), in the regulation of multiple cancers. However, the underlying mechanism of XIST in human hepatocellular carcinoma (HCC) still remains to be explored. Herein, intended to investigate the functional role of XIST in HCC initiation and progression. We first detected that XIST was significantly upregulated in HCC tissues and associated with tumor size and vascular invasion. Gain- and loss-of-function of XIST further presented that XIST promoted the progression of HCC cells, including proliferation, migration, and invasion. Moreover, silencing of XIST could inhibit tumor growth in vivo. We also found that XIST could target miR-194-5p and thus decrease miR-194-5p expression. Besides that, restoring XIST could reverse the inhibitory effect of miR-194-5p on the proliferation and invasion of HCC cells. We further elucidated such rescue role might through derepressing MAPK1 expression, the target of miR-194-5p. In brief, the above results elucidate the important role of XIST in HCC tumorigenesis, suggesting that XIST might be a candidate prognostic biomarker and a novel therapeutic target for treating HCC.

Achieve Location Privacy-Preserving Range Query in Vehicular Sensing.

Modern vehicles are equipped with a plethora of on-board sensors and large on-board storage, which enables them to gather and store various local-relevant data. However, the wide application of vehicular sensing has its own challenges, among which location-privacy preservation and data query accuracy are two critical problems. In this paper, we propose a novel range query scheme, which helps the data requester to accurately retrieve the sensed data from the distributive on-board storage in vehicular ad hoc networks (VANETs) with location privacy preservation. The proposed scheme exploits structured scalars to denote the locations of data requesters and vehicles, and achieves the privacy-preserving location matching with the homomorphic Paillier cryptosystem technique. Detailed security analysis shows that the proposed range query scheme can successfully preserve the location privacy of the involved data requesters and vehicles, and protect the confidentiality of the sensed data. In addition, performance evaluations are conducted to show the efficiency of the proposed scheme, in terms of computation delay and communication overhead. Specifically, the computation delay and communication overhead are not dependent on the length of the scalar, and they are only proportional to the number of vehicles.

Adrenalectomy does not improve survival rates of patients with solitary adrenal metastasis from non-small cell lung cancer.

BACKGROUND AND PURPOSE: Several case reports and studies have suggested that there is an increased survival rate for patients who undergo resection of solitary adrenal metastasis from non-small cell lung cancer (NSCLC). This study aimed to investigate whether NSCLC patients with solitary adrenal metastasis could gain a higher survival rate after adrenalectomy (ADX) when compared with those patients undergoing nonsurgical treatment, and to investigate the potential prognostic factors. PATIENTS AND METHODS: A total of 1,302 NSCLC inpatients' data from 2001 to 2015 were retrospectively reviewed to identify those with solitary adrenal metastasis. Overall survival for those who underwent both primary resection and ADX was compared to those patients with conservative treatment using the log-rank test. Potential prognostic variables were evaluated with univariate and multivariate analyses including clinical, therapeutic, pathologic, primary and metastatic data. RESULTS: A total of 22 NSCLC patients with solitary adrenal metastasis were identified, with an overall median survival of 11 months (95% confidence interval: 9.4-12.6 months) and a 1-year survival rate of 51.4% (95% confidence interval: 29.6%-73.2%). All of the patients had died by 30 months. There was no significant survival difference between patients who underwent primary and metastasis resection (n=10) and those treated conservatively (n=12), (P=0.209). Univariate analysis identified Eastern Cooperative Oncology Group performance status (ECOG PS) as the significant predictor of survival (P=0.024). Age (<65 vs ≥65 years), sex, pathologic type, mediastinal lymph node stage (N2 vs N0/N1), primary tumor size (<5 vs ≥5 cm), primary location (central vs peripheral), metastatic tumor size (<5 vs ≥5 cm), metastasis laterality, synchronous metastasis, and metastatic field radiotherapy were not identified as potential prognostic factors in relation to survival rate. In multivariate analysis, a stepwise selection procedure allowed both ECOG PS (P=0.007, relative risk =3.57) and pathologic type (P=0.069) to enter the Cox's hazard function. CONCLUSION: Primary and metastatic radical resection may not prolong the survival of NSCLC patients with solitary adrenal metastasis. ECOG PS and pathologic type might be the prognostic factors for these patients.

Clinical significance of day 5 peripheral blast clearance rate in the evaluation of early treatment response and prognosis of patients with acute myeloid leukemia.

BACKGROUND: Minimal residual disease detection in the bone marrow is usually performed in patients with acute myeloid leukemia undergoing one course of induction chemotherapy. To optimize the chemotherapy strategies, more practical and sensitive markers are needed to monitor the early treatment response during induction. For instance, peripheral blood (PB) blast clearance rate may be considered as such a monitoring marker. METHODS: PB blasts were monitored through multiparameter flow cytometry (MFC). Absolute counts were determined before treatment (D0) and at specified time points of induction chemotherapy (D3, D5, D7, and D9). The cut-off value of D5 peripheral blast clearance rate (D5-PBCR) was defined through receiver operating characteristic (ROC) analysis. Prognostic effects were compared among different patient groups according to D5-PBCR cut-off value. RESULTS: D5-PBCR cut-off value was determined as 99.55%. Prognostic analysis showed that patients with D5-PBCR ≥99.55% more likely achieved complete remission (94.6% vs. 56.1%, P < 0.001) and maintained a relapse-free status than other patients (80.56% vs. 57.14%, P = 0.027). Survival analysis revealed that relapse-free survival (RFS) and overall survival (OS) were longer in patients with D5-PBCR ≥99.55% than in other patients (two-year OS: 71.0% vs. 38.7%, P = 0.011; two-year RFS: 69.4% vs. 30.7%, P = 0.026). In cytogenetic-molecular intermediate-risk group, a subgroup with worse outcome could be distinguished on the basis of D5-PBCR (<99.55%; OS: P = 0.033, RFS: P = 0.086). CONCLUSIONS: An effective evaluation method of early treatment response was established by monitoring PB blasts through MFC. D5-PBCR cut-off value (99.55%) can be a reliable reference to predict treatment response and outcome in early stages of chemotherapy. The proposed marker may be used in induction regimen modification and help optimize cytogenetic-molecular prognostic risk stratification.