Cancer Expression Profiles Research Articles

Robust Metabolic Transcriptional Components in 34,494 Patient-Derived Samples and Cell Lines

Patient-derived bulk expression profiles of cancers can provide insight into transcriptional changes that underlie reprogrammed metabolism in cancer. However, these bulk profiles represent the average expression pattern of all heterogeneous tumor and non-tumor cells present in the biopsy. Therefore, subtle transcriptional footprints of metabolic processes can be concealed by other biological processes and experimental artifacts. We therefore performed consensus Independent Component Analyses (c-ICA) with 34,494 bulk expression profiles of patient-derived tumor biopsies, non-cancer tissues and cell lines. c-ICA enabled us to create a transcriptional metabolic landscape in which many robust metabolic transcriptional components (mTCs) and their activation score in individual samples were defined. Here we demonstrate that this metabolic landscape can be used to explore associations between metabolic processes and drug sensitivities, patient outcomes, and the composition of the immune tumor microenvironment. The metabolic landscape can be explored at http://www.themetaboliclandscapeofcancer.com.

Characterization and validation of long noncoding RNAs as new candidates in prostate cancer

BackgroundLong noncoding RNAs (lncRNAs) have been proved to be an important regulator in gene expression. In almost all kinds of cancers, lncRNAs participated in the process of pathogenesis, invasion, and metastasis. Meanwhile, compared with the large amounts of patients, there is rare knowledge about the role of lncRNAs in prostate cancer (PCa).Material/MethodIn this study, lncRNA expression profiles of prostate cancer were detected by Agilent microarray chip, 5 pairs of case and control specimens were involved in. Differentially expressed lncRNAs were screened out by volcano plot for constructing lncRNA-miRNA-mRNA central network. Then, the top ten up-regulated and down-regulated lncRNAs were validated by qRT-PCR in another 5 tumor specimens and 7 para-cancerous/benign contrasts. Furthermore, we searched for the survival curve of the top 10 upregulated and downregulated lncRNAs.ResultsA total of 817 differentially expressed lncRNAs were filtered out by the criteria of fold change (FC) and t-test p < 0.05. Among them, 422 were upregulated, whereas 395 were downregulated in PCa tissues. Gene ontology and KEGG pathway analyses showed that many lncRNAs were implicated in carcinogenesis. lnc-MYL2-4:1 (FC = 0.00141, p = 0.01909) and NR_125857 (FC = 59.27658, p = 0.00128) had the highest magnitude of change. The subsequent qPCR confirmed the expression of NR_125857 was in accordance with the clinical samples. High expression of PCA3, PCAT14 and AP001610.9 led to high hazard ratio while low expression of RP11-279F6.2 led to high hazard ratio.ConclusionsOur study detected a relatively novel complicated map of lncRNAs in PCa, which may have the potential to investigate for diagnosis, treatment and follow-up in PCa. Our study revealed the expression of NR_125857 in human PCa tissues was most up-regulated. Further studies are needed to investigate to figure out the mechanisms in PCa.

Atractyloside targets cancer-associated fibroblasts and inhibits the metastasis of colon cancer

BackgroundSeveral evidences have proved that cancer-associated fibroblasts (CAFs) play a crucial role in tumor progression. In fact, CAFs form a major component of tumor microenvironment (TME). Therefore, the development and metastasis of tumors can be effectively inhibited by small molecular compounds that target CAFs.MethodsIn this study, we mainly analyzed the expression profile of colon cancer (CC). We determined the intensity of CAFs in CC tissues by using the immune cell infiltration score. Gene enrichment analysis and the screening of differentially expressed genes were performed on the basis of the intensity of CAFs in CC tissues. We screened the small molecular compounds that were converted from differentially expressed genes. The results indicated that atractyloside was a small molecular compound related to CAFs in CC tissues. We identified the relationship between atractylosides and CAFs through target protein analysis and network analysis, and verified the inhibition effect of atractylosides on CC cells (CCC) by migration assay and scratch wound-healing assays.ResultsWe found that many target proteins of atractyloside, such as the matrix metalloproteinase family and integrin proteins, were related to the biological function of CAFs. By performing network analysis, we found that the target proteins FGF1, ITGB1, and EDNRA were closely related to tumor angiogenesis, while the target proteins MMP9 and ITGAV were correlated to an extracellular matrix (ECM) and cell motility. These findings which further confirmed the relationship between atractylosides and CAFs. In addition, transwell cell migration and scratch wound-healing assays proved that atractylosides could significantly inhibit the migration of CCCs.ConclusionsThe atractyloside might be a small molecular compound that potentially targets CAFs and inhibits the development as well as metastasis of CC by changing the TME.

Differences in Immune Gene Expression Profiles of Colorectal Cancer Between African-American and European-American Patients

Ramsay Camp, Ernest MD, FACS; Gerry, Brielle MD; Chung, Dongjun PhD; Findlay, Victoria PhD; Ford, Marvella PhD; Curran, Thomas MD Author Information

LINC00294 induced by GRP78 promotes cervical cancer development by promoting cell cycle transition.

Cervical cancer is one of the most common gynecological malignancies, and it has become a crucial public health problem. In the present study, the expression profiles of cervical cancer and normal cervical tissues were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Subsequently, the dysregulated long non-coding RNAs (lncRNAs) in cervical cancer were identified using R software Differentially expressed lncRNAs in cervical cancer that were associated with glucose-regulated protein 78 (GRP78) were screened out and the results demonstrated that eight lncRNAs were strongly positively correlated with GRP78. In order to confirm the relationship between GRP78 and candidate lncRNAs, GRP78 small interfering RNA (siRNA) was transfected into HeLa cells. The target lncRNAs that were regulated by GRP78 were then identified by reverse transcription-quantitative PCR and it was revealed that LINC00294 was significantly downregulated following GRP78-knockdown. Subsequently, Gene Set Enrichment Analysis demonstrated that LINC00294 was mainly enriched in regulating the cell cycle and the Hedgehog pathway. Following transfection of HeLa and SiHa cells with LINC00294 siRNA, the cell cycle was arrested at the G0/G1 phase. Western blotting suggested that LINC00294-knockdown downregulated the expression of cell cycle-associated factors (cyclin D, cyclin E and cyclin Dependent kinase 4) and upregulated cell cycle inhibitory factors (p16 and p21). The Hedgehog pathway was inhibited following knockdown of LINC00294 in HeLa and SiHa cells. In summary, LINC00294 induced by GRP78 promoted the progression of cervical cancer by regulating the cell cycle via Hedgehog pathway.

A ceRNA network and a potential regulatory axis in gastric cancer with different degrees of immune cell infiltration.

Immune cell infiltration is an important indicator of whether tumor patients will benefit from immunotherapy. Gastric cancer is one of the most common tumors in the world, and new indicators of immunotherapy are urgently needed. The aim of this study was to construct ceRNA networks in gastric cancer with different degrees of immune cell infiltration. We analyzed the expression profiles of different gastric cancer with different degrees of immune cell infiltration retrieved from The Cancer Genome Atlas (TCGA) database and found differentially expressed lncRNAs, mRNAs, and miRNAs. A ceRNA regulatory network of gastric cancer with different degrees of immune cell infiltration was constructed using functional annotation, RNA‐RNA interaction prediction, correlation analysis, survival analysis, and other comprehensive bioinformatics methods. The interaction and correlation between ceRNAs were verified using experiments on tumor tissues and cell lines. Cell line experiments showed a potential RP11‐1094M14.8/miR‐1269a/CXCL9 axis that was consistent with the ceRNA theory. qRT‐PCR results showed that RP11‐1094M14.8 knockdown significantly reduced the expression of CXCL9, and RP11‐1094M14.8 overexpression had the opposite effect. The results of clinical analysis of gastric cancer samples showed that RP11‐1094M14.8 and CXCL9 were highly expressed in hot tumors, and CXCL9 was positively correlated with a better prognosis for patients. The constructed novel ceRNA network and the potential regulatory axis may provide a comprehensive understanding of the potential mechanisms of development in gastric cancer with different degrees of immune cell infiltration. The RP11‐1094M14.8/miR‐1269a/CXCL9 axis may serve as a potential immune‐therapeutic target for gastric cancer with different degrees of immune cell infiltration.

Analysis of circular RNA expression profiles of lung cancer in Xuanwei, China.

BackgroundMounting evidence indicates that circular RNAs (circRNAs) could play a pivotal role in cancers. However, due to the lack of sensitive biomarkers, most lung cancer in Xuanwei (LCXW) patients are still diagnosed at an advanced stage accompany with distant metastasis.MethodsAccording to the stage of LCXW patients and tissue sources, circRNAs microarray detection was carried out in six groups. Considering fold change, raw intensity, the length of circRNAs, and P‐value, we selected eightcircRNAs for further study. A total of 50 paired LCXW tissues were carried out real‐time quantitative polymerase chain reaction (RT‐qPCR) in order to extended sample size to verify the expression of these circRNAs.ResultsWe designed 13 617 human circRNA probes for the human circular RNA microarray, detected 10 819 circRNA in six groups of samples; 537 circRNAs were differentially expressed consistently in every stage. Through RT‐qPCR, we selected 8 circRNAs, three of which were upregulated (hsa_circ_0005927, hsa_circ_0069397 and hsa_circ_0000937) and five were downregulated (hsa_circ_0001936, hsa_circ_0005255, hsa_circRNA_406010, hsa_circ_0007064, hsa_circ_0000907) in tumor tissues, only hsa_circ_0001936 showed the opposite expression between microarray and RT‐qPCR, others were consistent. Additionally, hsa_circ_0005927 and hsa_circ_0001936 were significantly correlated with tumor size, and hsa_circRNA_406010 was related to the prognosis of LCXW patients.ConclusionTogether, these results suggest that hsa_circ_0005927, hsa_circ_0001936, and hsa_circRNA_406010 may serve as the novel potential biomarkers for LCXW. Moreover, these results may provide a new insight for the pathogenesis of LCXW.

Actin-Associated Gene Expression is Associated with Early Regional Metastasis of Tongue Cancer.

We aimed to analyze gene expression profile of tongue cancer associated with early lymph node metastasis using the cancer genome atlas (TCGA) data. Basic research. A total of 515 patients with matched RNAseq data of primary tumor and clinical data from TCGA data were extracted. To compare gene expression profile between early T-stage tongue cancer with cervical lymph node metastasis and late T-stage tongue cancer without cervical metastasis, genomic data of following two groups was assessed; 1) group 1: T1/2 and N2/3 (n = 41), 2) group 2: T4 and N0 (n = 65). Using R and limma package in bioconductor program, differentially expressed genes (DEGs) were extracted. Gene ontology and pathway enrichment analysis were performed using the DAVID online tool. FFPE tissue of 285 patients were evaluated for the validation of relevant genes by imunofluorescence (IF) and immunohistochemical (IHC) stain. A total of 225 DEGs were found, and 50 genes were highly significant with absolute fold change over eight. Gene ontology and pathway enrichment analysis revealed that most of the upregulated genes were associated with actin cytoskeleton and included following genes: ANKRD23, NO3, PDLIM3, MUSTN1, TNNT3, MYBPC1, MB, MYH3, TTN, ACTA1, and ACTC1. When comparing tongue cancer with cN0pN0 vs. pN0pN+ using the total tongue cancer cohort of TCGA, ACTA1 was the only parameter which was associated with hidden lymph node metastasis in T1/2 (P = .019). Perineural invasion was significantly associated with high expression of ACTA1 (P < .001). IF and IHC analysis revealed that actin was overexpressed, while E-cadherin and N-cadherin were not significantly different. Actin associated genes, especially overexpression of ACTA1 may be associated with early regional metastasis of tongue cancer. 3 Laryngoscope, 131:813-819, 2021.

Transcriptome analysis reveals key signature genes involved in the oncogenesis of lung cancer.

Previous studies have suggested potential signature genes for lung cancer, however, due to factors such as sequencing platform, control, data selection and filtration conditions, the results of lung cancer-related gene expression analysis are quite different. Here, we performed a meta-analysis on existing lung cancer gene expression results to identify Meta-signature genes without noise. In this study, functional enrichment, protein-protein interaction network, the DAVID, String, TfactS, and transcription factor binding were performed based on the gene expression profiles of lung adenocarcinoma and non-small cell lung cancer deposited in the GEO database. As a result, a total of 574 differentially expressed genes (DEGs) affecting the pathogenesis of lung cancer were identified (207 up-regulated expression and 367 down-regulated expression in lung cancer tissues). A total of 5,093 interactions existed among the 507 (88.3%) proteins, and 10 Meta-signatures were identified: AURKA, CCNB1, KIF11, CCNA2, TOP2A, CENPF, KIF2C, TPX2, HMMR, and MAD2L1. The potential biological functions of Meta-signature DEGs were revealed. In summary, this study identified key genes involved in the process of lung cancer. Our results would help the developing of novel biomarkers for lung cancer.

Dissecting expression profiles of gastric precancerous lesions and early gastric cancer to explore crucial molecules in intestinal-type gastric cancer tumorigenesis.

Intestinal‐type gastric cancer (IGC) has a clear and multistep histological evolution. No studies have comprehensively explored gastric tumorigenesis from inflammation through low‐grade intraepithelial neoplasia (LGIN) and high‐grade intraepithelial neoplasia (HGIN) to early gastric cancer (EGC). We sought to investigate the characteristics participating in IGC tumorigenesis and identify related prognostic information within the process. RNA expression profiles of 94 gastroscopic biopsies from 47 patients, including gastric precancerous lesions (GPL: LGIN and HGIN), EGC, and paired controls, were detected by Agilent Microarray. During IGC tumorigenesis from LGIN through HGIN to EGC, the number of activity‐changed tumor hallmarks increased. LGIN and HGIN had similar expression profiles when compared to EGC. We observed an increase in the stemness of gastric epithelial cells in LGIN, HGIN, and EGC, and we found 27 consistent genes that might contribute to dedifferentiation, including five driver genes. Remarkably, we perceived that the immune microenvironment was more active in EGC than in GPL, especially in the infiltration of lymphocytes and macrophages. We identified a five‐gene signature from the gastric tumorigenesis process that could independently predict the overall survival and disease‐free survival of GC patients (log‐rank test: p < 0.0001), and the robustness was verified in an independent cohort (n > 300) and by comparing with two established prognostic signatures in GC. In conclusion, during IGC tumorigenesis, cancer‐like changes occur in LGIN and accumulate in HGIN and EGC. The immune microenvironment is more active in EGC than in LGIN and HGIN. The identified signature from the tumorigenesis process has robust prognostic significance for GC patients. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Identification of key miRNAs in the progression of hepatocellular carcinoma using an integrated bioinformatics approach.

BackgroudIt has been shown that aberrant expression of microRNAs (miRNAs) and transcriptional factors (TFs) is tightly associated with the development of HCC. Therefore, in order to further understand the pathogenesis of HCC, it is necessary to systematically study the relationship between the expression of miRNAs, TF and genes. In this study, we aim to identify the potential transcriptomic markers of HCC through analyzing common microarray datasets, and further establish the differential co-expression network of miRNAs–TF–mRNA to screen for key miRNAs as candidate diagnostic markers for HCC.MethodWe first downloaded the mRNA and miRNA expression profiles of liver cancer from the GEO database. After pretreatment, we used a linear model to screen for differentially expressed genes (DEGs) and miRNAs. Further, we used weighed gene co-expression network analysis (WGCNA) to construct the differential gene co-expression network for these DEGs. Next, we identified mRNA modules significantly related to tumorigenesis in this network, and evaluated the relationship between mRNAs and TFs by TFBtools. Finally, the key miRNA was screened out in the mRNA–TF–miRNA ternary network constructed based on the target TF of differentially expressed miRNAs, and was further verified with external data set.ResultsA total of 465 DEGs and 215 differentially expressed miRNAs were identified through differential genes expression analysis, and WGCNA was used to establish a co-expression network of DEGs. One module that closely related to tumorigenesis was obtained, including 33 genes. Next, a ternary network was constructed by selecting 256 pairs of mRNA–TF pairs and 100 pairs of miRNA–TF pairs. Network mining revealed that there were significant interactions between 18 mRNAs and 25 miRNAs. Finally, we used another independent data set to verify that miRNA hsa-mir-106b and hsa-mir-195 are good classifiers of HCC and might play key roles in the progression of HCC.ConclusionOur data indicated that two miRNAs—hsa-mir-106b and hsa-mir-195—are identified as good classifiers of HCC.

73P microRNA expression profiles of single hormone receptor-positive breast cancers

The molecular landscape of single hormone receptor-positive breast cancers – ER(+)/PgR(-) and ER(-)/PgR(+), remains vague. Clinically, endocrine sensitivity and prognosis of these tumors are believed to be intermediate between ER(+)/PgR(+) and double-negative cancers. MicroRNAs (miRNAs) emerge as important players in breast cancer biology and may serve as potential therapeutic targets. In the current study, we aimed to compare the miRNA expression profiles of these cancers.

Application of the chemokine-chemokine receptor axis increases the tumor-targeted migration ability of cytokine-induced killer cells in patients with colorectal cancer.

Cytokine-induced killer (CIK) cells are a group of heterogeneous immune cells which can be isolated from human peripheral blood mononuclear cells and have demonstrated therapeutic benefit both in hematologic malignancies and solid tumors, including colorectal cancer. However, poor tumor-targeted migration has limited the clinical efficacy of CIK cell treatment. The chemokine-chemokine receptor (CK-CKR) axis serves a role in the tumor-directed trafficking capacity of immune cells. Investigating the relationship between CKR profiles on the surface of CIK cells and chemokine expression levels in the tumor microenvironment may improve CIK cell therapy. In the present study, the spectrum of chemokine expression levels in tumor tissues from patients with colorectal cancer (CRC) and CKR expression profiles in CIK cells obtained from the same individuals with CRC were investigated. The results showed that chemokine expression levels in tumor tissues exhibited variability and cell line heterogeneity. However, the expression levels of a number of chemokines were similar in different CRC donors and cell lines. Expression levels of CXCLL10, CXCL11 and CCL3 were significantly higher in most tumor tissues compared with adjacent normal tissues and highly expressed in most CRC cell lines. In accordance with chemokine expression levels, CKR profiles on the surface of CIK cells also showed donor-to-donor variability. However, concordant expression profiles of CKRs were identified in different patients with CRC. CXCR3 and CXCR4 were highly expressed on the surface of CIK cells through the culture process. Importantly, the expression levels of all CKRs, especially CCR4, CXCR4 and CXCR3, were notably decreased during the course of CIK cell expansion. The changing trend of CKR profiles were not correlated with the chemokine expression profiles in CRC tissues (CCL3, CXCL12 and CXCL10/CXCL11 were highly expressed in CRC tissue). Re-stimulating CIK cells using chemokines (CCL21 and CXCL11) at the proper time point increased corresponding CKR expression levels on the surface of CIK cells and enhance tumor-targeted trafficking in vitro. These results demonstrated that modification of the CK-CKR axis using exogenous recombinant chemokines at the proper time point enhanced CIK cell trafficking ability and improved CIK antitumor effects.

Acetyl-11-keto-β-boswellic Acid Inhibits Precancerous Breast Lesion MCF-10AT Cells via Regulation of LINC00707/miR-206 that Reduces Estrogen Receptor-α.

PurposeAcetyl-11-keto-β-boswellic acid (AKBA) has therapeutic effects on a range of diseases, including tumours. lncRNAs, as competing endogenous RNAs (ceRNAs), can interact with miRNAs to regulate the expression of target genes, which can affect the development of tumors. Here, we examined the effects of AKBA on breast precancerous lesions MCF-10AT cells.MethodsThe expression profiles of breast cancer (BC) tissue were collated from The Cancer Genome Atlas (TCGA), and the lncRNA-miRNA-mRNA ceRNA network was constructed. AKBA targets were predicted by network pharmacology. The expression of long intergenic nonprotein-coding RNA 707 (LINC00707), miR-206 and ER-α was determined by qRT-PCR. Cell viability, apoptosis and cycle were assessed by CCK-8 and flow cytometry. Protein levels were measured by Western blotting.ResultsA total of 3205 differentially expressed mRNAs, 104 miRNAs, and 605 lncRNAs were identified. The ceRNA network consisting of 9 lncRNAs, 15 miRNAs and 82 mRNAs was constructed. We found that LINC00707 was up-regulated and miR-206 was down-regulated in MCF-10AT cells. Transfected si-LINC00707 could inhibit cell proliferation, induce cell apoptosis and cycle arrest of MCF-10AT cells. In addition, network pharmacology predicted that AKBA may regulate the ESR1 in the treatment of BC. Our research demonstrated that AKBA could induce cell apoptosis and G1-phase arrest and inhibit ER-α expression via LINC00707/miR-206 in MCF-10AT cells.ConclusionAKBA inhibited MCF-10AT cells via regulation of LINC00707/miR-206 that reduces ER-α.

Circular RNA hsa_circ_0075828 Promotes Bladder Cancer Cell Proliferation Through Activation of CREB1

Circular RNAs (circRNAs), one kind of non-coding RNA, have been reported as critical regulators for modulating gene expression in cancer. In this study, microarray analysis was used to screen circRNA expression profiles of bladder cancer (BC) 5637 cells, T24 cells and normal control SV-HUC-1 cells. The data from the microarray showed that hsa_circ_0075828 (named circCASC15) was most highly expressed in 5637 and T24 cells. circCASC15 was highly expressed in BC tissues and cells. Overexpression of circCASC15 was closely associated with BC tumor stage and promoted cell proliferation significantly in vitro and in vivo. Mechanistically, circCASC15 could act as miR-1224-5p sponge to activate the expression of CREB1 to promote cell proliferation in BC. In short, circCASC15 promotes cell proliferation in BC, which might be a new molecular target for BC diagnosis and therapy.

Screening of characteristic biomolecules related to bladder cancer based on construction of ceRNA regulation network.

The purpose of this study is to screen bladder cancer-associated biomarkers by combining lncRNA, miRNA, and mRNA expression profile of bladder cancer, and to explore bladder cancer-associated tumor markers by constructing a ceRNA regulation network. Bladder cancer mRNA and miRNA samples were downloaded from the TCGA database; the lncRNA and mRNA detected in the RNA-seq expression profile were identified using the HUGO Gene Nomenclature Committee database. Screening for significant differentially expressed RNA resulted in 1693 mRNAs, 66 lncRNAs, and 130 miRNAs. Then, the significant differently expressed RNAs from the screening were subjected to annotation analysis of GO functional nodes and KEGG signaling pathways. A ceRNA regulation network consisting of lncRNA-miRNA-mRNA was constructed by synthesizing lncRNA-miRNA and miRNA-mRNA. Finally, a ceRNA regulation network consisting of two lncRNAs, one miRNA, and three mRNAs was obtained. KM remodeling curve analysis was performed for each factor. In bladder cancer tumor samples, samples down-regulated by LINC01198, PPTRD-AS1, has-miR-216a, SEMA3D, EPHA5, and DCLK1 had a good overall survival prognosis, indicating that these several characteristic target molecules were found to be high-risk factors for bladder cancer tumors.

NOS1 expression promotes proliferation and invasion and enhances chemoresistance in ovarian cancer.

Nitric oxide (NO), an important chemical messenger, serves a dual role in tumor progression. Nitric oxide synthase isoform 1 (NOS1) was observed to be increasingly expressed in various types of cancer, and its expression has been associated with tumor progression. However, the level of NOS1 expression and the associated functions of NOS1 in human ovarian cancer remain undefined. Using gene expression profiles of ovarian cancer from the Gene Expression Omnibus (GEO) database, the present study revealed that NOS1 was increasingly expressed in ovarian cancer tissues. The present study investigated the level of NOS1 expression and its effects on in vitro cell function, including proliferation, migration and invasion as well as chemoresistance to cispatin (DDP) treatment in OVCAR3 cells. Reverse transcription-quantitative polymerase chain reaction demonstrated that the level of NOS1 mRNA expression varied in different ovarian cancer lines. However, immunoblotting indicated that the level of NOS1 protein expression was constitutively high in ovarian cancer cell lines. Treatment with NOS inhibitor NG-nitro-L-arginine methyl ester or transfection with NOS1 short hairpin RNA significantly inhibited cell proliferation, migration and invasion compared with the control, whereas the sensitivity of OVCAR3 cells to DDP treatment was increased. The results of the present study indicated that NOS1 promoted the function of ovarian cancer cells, including proliferation, invasion and chemoresistance, providing a potential target for ovarian cancer therapeutic.

FENDRR Sponges miR-424-5p to Inhibit Cell Proliferation, Migration and Invasion in Colorectal Cancer.

Objective:LncRNAs are non-coding RNAs exerting vital roles in the occurrence and development of various cancer types. This study tended to describe the expression pattern of FENDRR in colorectal cancer (CRC), and further investigate the role of FENDRR in CRC cell biological behaviors.Methods:Gene expression profile of colon cancer was accessed from the TCGA database, and then processed for differential analysis for identification of differentially expressed lncRNAs and miRNAs. Some in vitro experiments like qRT-PCR, MTT, colony formation assay, wound healing assay and Transwell assay were performed to assess the effect of FENDRR on cell biological behaviors. Dual-luciferase reporter assay was conducted to further validate the targeting relationship between FENDRR and miR-424-5p, and rescue experiments were carried out for determining the mechanism of FENDRR/miR-424-5p underlying the proliferation, migration and invasion of CRC cells.Results:Bioinformatics analysis suggested that FENDRR was significantly down-regulated in CRC tissue, and low FENDRR was intimately correlated to poor prognosis. FENDRR overexpression could greatly inhibit cell proliferation, migration and invasion. Besides, there was a negative correlation between FENDRR and miR-424-5p. Dual-luciferase reporter assay indicated that miR-424-5p was a direct target of FENDRR. Rescue experiments discovered that FENDRR exerted its role in cell proliferation, migration and invasion in CRC via targeting miR-424-5p.Conclusion:FENDRR is poorly expressed in CRC tissue and cells, and low FENDRR is responsible for the inhibition of cell proliferation, migration and invasion of CRC by means of targeting miR-424-5p.

Prognostic gene expression signature revealed the involvement of mutational pathways in cancer genome.

Background: Over the years, many efforts have been made to use the gene expression profiles of cancer types/subtypes to identify the prognostic genes with their potential clinical applications. However, one major challenge remains is to predict the common prognostic genes using simultaneously the dataset of multiple cancers, especially by considering the differences in survival, expression and the associated mutated pathways.Methods: Herein, we carried out a comprehensive examination for the prognostic genes and linked them to the mutational status of 29 cancers, so as to find independent prognostic genes and mechanisms. Additionally, their diagnostic value of them was also assessed. Results: our extensive analysis revealed: 1) the number of prognostic and diagnostic genes differs greatly across the cancers, 2) the potentially implicated 22 genes harbor the diagnostic as well as prognostic capacity, 3) the universal prognostic genes (CDC20, CDCA8, ASPM, ERCC6L, and GTSE1) were found to be involved in the spindle assembly checkpoint, 4) the prognostic genes were found to be statistically linked to the frequently mutated TP53-, MAPK-, PI3K- and AKT- related pathways. We also manually mined possible biological mechanisms for some of the statistical links in literatures.Conclusions: Taken together, we identified the prognostic genes and in addition we assessed their diagnostic capacity. Our analysis provides an important insight about the considerable overlapping between gene expression variation and the further associated altered mutational pathways across the cancer genome. We thus hypothesized that cancer related (mutated) genes are tightly connected and are capable to reshape the genome in multiple cancer types.

A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma.

Pancreatic cancer expression profiles largely reflect a classical or basal-like phenotype. The extent to which these profiles vary within a patient is unknown. We integrated evolutionary analysis and expression profiling in multiregion-sampled metastatic pancreatic cancers, finding that squamous features are the histologic correlate of an RNA-seq-defined basal-like subtype. In patients with coexisting basal and squamous and classical and glandular morphology, phylogenetic studies revealed that squamous morphology represented a subclonal population in an otherwise classical and glandular tumor. Cancers with squamous features were significantly more likely to have clonal mutations in chromatin modifiers, intercellular heterogeneity for MYC amplification and entosis. These data provide a unifying paradigm for integrating basal-type expression profiles, squamous histology and somatic mutations in chromatin modifier genes in the context of clonal evolution of pancreatic cancer.