RESUMO
PURPOSE: Prostate cancer is among the most central sources of cancer-related mortalities. In order to find novel candidates for therapeutic strategies in this kind of cancer, we developed an in-silico method for identification of competing endogenous RNA network. METHODS: According to the microarray data analyses between prostate tumor and normal specimens, we attained 1312 differentially expressed (DE)mRNAs, including 778 down-regulated DEmRNAs (such as CXCL13 and BMP5) and 584 up-regulated DEmRNAs (such as OR51E2 and LUZP2), 39 DElncRNAs, including 10 down-regulated DElncRNAs (such as UBXN10-AS1 and FENDRR) and 29 up-regulated DElncRNAs (such as PCA3 and LINC00992) and 10 DEmiRNAs, including 2 down-regulated DEmiRNAs (such as MIR675 and MIR1908) and 8 up-regulated DEmiRNAs (such as MIR6773 and MIR4683). RESULTS: We constructed the ceRNA network between these transcripts. We also evaluated the related signaling pathways and the significance of these RNAs in prediction of survival of patients with prostate cancer. CONCLUSION: This study provides novel candidates for construction of specific treatment routes for prostate cancer.
Assuntos
MicroRNAs , Neoplasias da Próstata , RNA Longo não Codificante , Receptores Odorantes , Masculino , Humanos , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Endógeno Competitivo , Redes Reguladoras de Genes , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/metabolismoRESUMO
The interaction between long non-coding RNAs (lncRNAs), miRNAs and mRNAs has implications in the pathogenesis of different cancer, including breast cancer. In the current study, we developed an in-silico approach to ascertain the competing endogenous RNA (ceRNA) network in breast cancer. Our approach led to identification of 1816 differentially expressed (DE) mRNAs, including 1039 downregulated DEmRNAs (such as LEP and ADIPOQ) and 777 upregulated DEmRNAs (such as COL11A1 and COL10A1), 19 DElncRNAs, including 15 downregulated DElncRNAs (such as CARMN and COPG2IT1) and 4 upregulated DElncRNAs (such as MALAT1 and NRAV) and 27 DEmiRNAs, including 15 downregulated DEmiRNAs (such as MIR452 and MIR224) and 12 upregulated DEmiRNAs (such as MIR6787 and MIR21). Pathway analysis revealed down-regulation of PPAR, Fatty acid metabolism, Adipocytokine, Vascular smooth muscle contraction and Metabolism of xenobiotics by cytochrome P450, while up-regulation of Pyrimidine metabolism, p53 signaling pathway, Cell cycle, Oocyte meiosis and RNA transport pathways in breast cancer. Finally, we constructed an lncRNA/miRNA/mRNA ceRNA network consisted of 2 lncRNAs, 15 mRNAs, and 4 miRNAs. This network represents an appropriate target for design of anti-cancer modalities and documentation of novel markers for breast cancer.
Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Humanos , Feminino , Biologia de Sistemas , Neoplasias da Mama/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Redes Reguladoras de Genes/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação Neoplásica da Expressão Gênica/genéticaRESUMO
MicroRNA-328 (miR-328) is an RNA gene that is primarily associated with lung cancer, and its encoding gene is located on 16q22.1. Expression of miR-328 has been observed in lung and esophagus tissues based on RNAseq data. Although several studies have aimed at the detection of miR-328 levels in tumor tissues, there is an obvious discrepancy between the results of these studies. Even in a certain type of cancer, some studies have reported up-regulation of miR-328 in cancerous tissues versus control tissues, while others have reported its down-regulation. This discrepancy might be attributed to different stages/grades of tumor tissues or other clinical characteristics. This review article focuses on the available literature to explore the functions of miR-328 in the development of human carcinogenesis.
Assuntos
Neoplasias Pulmonares , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pulmonares/patologia , Regulação para Cima , Regulação para Baixo , Carcinogênese/genética , Carcinogênese/patologia , Regulação Neoplásica da Expressão Gênica/genética , Linhagem Celular Tumoral , Proliferação de Células/genéticaRESUMO
Breast cancer is a genetically heterogeneous disorder associated with dysregulation of several genes. Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent transcription factor that is expressed by many tumoral cells such as transformed breast cancer cells. We investigated expressions of nine PPARγ-related lncRNAs, namely KCNIP2-AS1, TRHDE-AS1, FAM13A-AS1, ALDH1A1-AS2, SH3BP5-AS1, HID1-AS1, LINC01140, LIPE-AS1 and ABCA9-AS1 in paired breast cancer samples and non-tumoral tissues. Expression assays showed lower expression levels of TRHDE-AS1, ALDH1L1-AS2, KCNIP2-AS1, ABCA9-AS1, LIPE-AS1 and LINC01140 in tumoral compared with non-tumoral samples. The mentioned genes could differentiate between breast tumors and non-tumoral samples with AUC values ranging from 0.77 to 0.62 for LINC01140 and LIPE-AS1, respectively. The highest specificity and sensitivity values were reported for KCNIP2-AS1 and LINC01140, respectively. Significant correlations were reported between all pairs of genes in both tumoral and non-tumoral tissues. The most robust ones were between ABCA9-AS1 and KCNIP2-AS1 (correlation coefficient=0.85) in non-tumoral tissues and between LIPE-AS1 and TRHDE-AS1 (correlation coefficient=0.83) in tumoral tissues. There was a significant negative association between expression levels of KCNIP2-AS1 gene in tumor tissues and different histological grades. Besides, there was a significant negative association between expression levels of FAM13A-AS1, KCNIP2-AS1and LIPE-AS1 genes in tumor tissues and different mitotic rates. Taken together, PPARγ-related lncRNAs might be regarded as potential contributors to the pathogenesis of breast cancer.
Assuntos
Neoplasias da Mama , RNA Longo não Codificante , Feminino , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Regulação Neoplásica da Expressão Gênica/genética , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Colorectal cancer (CRC) is the third most frequent cancer to be diagnosed in both females and males necessitating identification of effective biomarkers. An in-silico system biology approach called weighted gene co-expression network analysis (WGCNA) can be used to examine gene expression in a complicated network of regulatory genes. In the current study, the co-expression network of DEGs connected to CRC and their target genes was built using the WGCNA algorithm. GO and KEGG pathway analysis were carried out to learn more about the biological role of the DEmRNAs. These findings revealed that the genes were mostly enriched in the biological processes that were involved in the regulation of hormone levels, extracellular matrix organization, and extracellular structure organization. The intersection of genes between hub genes and DEmRNAs showed that DKC1, PA2G4, LYAR and NOLC1 were the clinically final hub genes of CRC.
Assuntos
Biologia , Neoplasias Colorretais , Feminino , Masculino , Humanos , Genes Reguladores , Algoritmos , Perfilação da Expressão Gênica , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Proteínas Nucleares , Proteínas de Ciclo Celular , Proteínas de Ligação a RNA , Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Ligação a DNARESUMO
Non-functioning pituitary adenomas (NFPAs) are a group of pituitary tumors lacking manifestations linked to high hormone production, such as acromegaly and Cushing's syndrome. NFPA carcinogenesis depends on several molecular players. Long non-coding RNAs (lncRNAs) are a class of molecular players whose role in tumorigenesis has just recently been recognized. In the current study, we appraised expressions of 5 lncRNAs, namely FGD5-AS1, ATP6V0E2-AS1, ARHGAP5-AS1, WWC2-AS2 and EPB41L4A-AS1 in NFPAs versus their corresponding non-tumoral samples. Expressions of ATP6V0E2-AS1, EPB41L4A-AS1, FGD5-AS1 and WWC2-AS2 were significantly increased in NFPA samples compared with adjacent non-tumoral samples (P values = 0.037, 0.007, 0.008 and 0.03, respectively). However, expression of ARHGAP5-AS1 was not different between NFPA samples and controls (P value = 0.62). EPB41L4A-AS1 and FGD5-AS1 could discriminate between NFPA samples and adjacent non-tumoral samples (P values = 0.03 and 0.04, respectively). However, the AUC values were not appropriate. There was a significant positive association between age of NFPA patients and invasiveness of NFPA (χ2 = 4.24, P value = 0.039). Moreover, there was a significant positive association between diseases duration and CSF leak (χ2 = 11.4, p value = 0.023). Finally, there was a significant positive association between tumor size and Knosp classification (χ2 = 11.5, p value = 0.02) and invasiveness of NFPA (χ2 = 6.12, p value = 0.04). The current study provides information about dysregulation of lncRNAs in NFPAs and warrants additional studies in this field.
Assuntos
Adenoma , Neoplasias Hipofisárias , RNA Longo não Codificante , Humanos , Neoplasias Hipofisárias/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Adenoma/patologiaRESUMO
LINC00174 is an example of long intergenic non-coding RNAs with important functions in the development of human cancers. The gene encoding this lincRNA is located on 7q11.21. LINC00174 has been demonstrated to play an oncogenic role in a variety of cancers, including colorectal carcinoma, thymic carcinoma, glioma, glioblastoma, hepatocellular carcinoma, kidney renal clear cell carcinoma, breast cancer and non-functioning pituitary adenoma. In lung cancer, there is an obvious discrepancy between different studies regarding the role of this lincRNA. This lincRNA is also involved in the determination of prognosis of different cancers, particularly colorectal cancer. In the current review, we discuss the role of this lincRNA in human carcinogenesis based on the available data in the literature and bioinformatics tools.
Assuntos
Carcinoma Hepatocelular , Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Hepáticas , RNA Longo não Codificante , Neoplasias do Timo , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma de Células Renais/genética , Biologia Computacional , Neoplasias Hepáticas/genética , Neoplasias Renais/genética , Regulação Neoplásica da Expressão GênicaRESUMO
Pancreatic ductal adenocarcinoma (PDAC) is a cancer that is usually diagnosed at late stages. This highly aggressive tumor is resistant to most therapeutic approaches, necessitating identification of differentially expressed genes to design new therapies. Herein, we have analyzed single cell RNA-seq data with a systems biology approach to identify important differentially expressed genes in PDAC samples compared to adjacent non-cancerous samples. Our approach revealed 1462 DEmRNAs, including 1389 downregulated DEmRNAs (like PRSS1 and CLPS) and 73 upregulated DEmRNAs (like HSPA1A and SOCS3), 27 DElncRNAs, including 26 downregulated DElncRNAs (like LINC00472 and SNHG7) and 1 upregulated DElncRNA (SNHG5). We also listed a number of dysregulated signaling pathways, abnormally expressed genes and aberrant cellular functions in PDAC which can be used as possible biomarkers and therapeutic targets in this type of cancer.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Biologia de Sistemas , Perfilação da Expressão Gênica , Células Endoteliais/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Análise de Sequência de RNA , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias PancreáticasRESUMO
Long Intergenic Non-Protein Coding RNA 511 (LINC00511) is an RNA gene being mostly associated with lung cancer. Further assessments have shown dysregulation of this lncRNA in a variety of cancers. LINC00511 has interactions with hsa-miR-29b-3p, hsa-miR-765, hsa-mir-150, miR-1231, TFAP2A-AS2, hsa-miR-185-3p, hsa-miR-29b-1-5p, hsa-miR-29c-3p, RAD51-AS1 and EZH2. A number of transcription factors have been identified that regulate expression of LINC00511. The current narrative review summarizes the role of LINC00511 in different cancers with an especial focus on its prognostic impact in human cancers.
RESUMO
Long non-coding RNAs (lncRNAs) have been shown to be dysregulated in a variety of malignant and non-malignant lesions including non-functioning pituitary adenomas (NFPAs). In the current experimental study, we have selected six lncRNAs, namely MAPKAPK5-AS1, NUTM2B-AS1, ST7-AS1, LIFR-AS1, PXN-AS1 and URB1-AS1 to assess their expression in a cohort of Iranian patients with NFPA. MAPKAPK5-AS1, PXN-AS1 and URB1-AS1 were shown to be over-expressed in NFPA tissues compared with control samples (Expression ratios (95% CI) = 10 (3.94-25.36), 11.22 (4.3-28.8) and 9.33 (4.12-21.12); p values < 0.0001, respectively). The depicted ROC curves showed the AUC values of 0.73, 0.80 and 0.73 for MAPKAPK5-AS1, PXN-AS1 and URB1-AS1, respectively. Relative expression level of PXN-AS1 was associated with tumour subtype (p value = 0.49). Besides, relative expression levels of MAPKAPK5-AS1 and LIFR-AS1 were associated with gender of patients (p values = 0.043 and 0.01, respectively). Cumulatively, the current study indicates the possible role of MAPKAPK5-AS1, PXN-AS1 and URB1-AS1 lncRNAs in the pathogenesis of NFPAs.
Assuntos
Neoplasias Hipofisárias , RNA Longo não Codificante , Humanos , Regulação para Cima/genética , RNA Longo não Codificante/genética , Neoplasias Hipofisárias/genética , Irã (Geográfico) , Regulação Neoplásica da Expressão Gênica , Proteínas Nucleares , PaxilinaRESUMO
The Rho GTPases have prominent roles in cell cycle transition and cell migration. Some members of this family have been found to be mutated in cancers. Moreover, alterations in expression levels and/or activity of these proteins have been reported in many types of cancers. Thus, Rho GTPases are involved in the carcinogenesis. Rho GTPases regulate growth, motility, invasiveness and metastatic ability of breast cancer cells. Long non-coding RNAs (lncRNAs) have been revealed to exert significant effect in the regulation of these proteins via direct routes or through sequestering microRNAs that inhibit Rho GTPases. We aimed to assess expression levels of four Rho GTPase-related lncRNAs, namely NORAD, RAD51-AS1, NRAV and DANCR in breast cancer samples versus non-cancerous specimens from the same individuals. Expression levels of NORAD were shown to be elevated in tumoral tissues compared with non-tumoral tissues (Expression ratio (95% CI)= 5.85 (3.16-10.83), Standard error of mean (SEM)= 0.44, P value< 0.0001). NRAV expression was also higher in tumoral tissues compared with control tissues (Expression ratio=2.85 (1.52-5.35), SEM= 0.45, P value= 0.0013). Similar to these lncRNAs, RHOA was demonstrated to be up-regulated in malignant tissues (Expression ratio=6.58 (3.17-13.63), SEM= 0.52, P value< 0.0001). Although expression ratio values showed up-regulation of RAD51-AS1 and DANCR in cancerous tissues (Expression ratio (95% CI)= 2.2 (1.05-4.6) and 1.35 (0.72-2.53), respectively), P values did not reach significance level (P values=0.0706 and 0.3746, respectively). There were significant associations between expression level of NRAV gene in tumor tissues and a number of parameters including age, histological tumor grade and tubule formation. Taken together, the current study shows dysregulation of a number of RHOA-related lncRNAs in breast cancer in association with abnormal up-regulation of this member of Rho GTPase family and suggests conduction of additional functional studies to unravel their mode of participation in the breast carcinogenesis.
Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Humanos , Feminino , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , MicroRNAs/genética , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica/genética , Linhagem Celular TumoralRESUMO
Colorectal Neoplasia Differentially Expressed (CRNDE) is an lncRNA with crucial roles in cancer development. It is located on chromosome 16 on the opposite strand to the adjacent IRX5 gene, implying the presence of a shared bidirectional promoter for these two genes. Expression of CRNDE has been assessed in a diverse array of hematological malignancies and solid tumors, representing its potential as a therapeutic target in these conditions. This lncRNA has a regulatory effect on activity of several pathways and axes that are involved in the regulation of cell apoptosis, immune responses and tumorigenesis. The current review is an updated review about the role of CRNDE in the development of cancers.
Assuntos
MicroRNAs , Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , Apoptose/genética , Proliferação de Células/genética , MicroRNAs/genética , Neoplasias/genéticaRESUMO
Long intergenic non-protein coding RNA 173 (LINC00173) is a long non-coding RNA with especial function in the tumorigenic process. Studies in different types of cancers support an oncogenic role for LINC00173 except for studies in B-cell precursor acute lymphoblastic leukemia, cervical cancer, pancreatic cancer and gastric cancer. In breast and lung cancers, both oncogenic and tumor suppressor roles have been reported for LINC00173. LINC00173 can serve as a molecular sponge for miRNAs. miR-218/Etk, miR-511-5p/VEGFA, miR-182-5p/AGER, miR-765/NUTF2, miR-765/PLP2, miR-182-5p/FBXW7, miR-338-3p/Rab25, miR641/RAB14 and miR-1275/BCL2 are examples of the miRNA/mRNA axes being regulated by LINC00173 in the context of cancer. The current review provides a summary of different studies on the role of LINC00173 in these cancers.
Assuntos
Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Humanos , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Neoplasias Pulmonares/patologia , Genes Supressores de Tumor , Carcinogênese/genética , Proliferação de Células/genética , RNA Longo não Codificante/genética , Proteínas rab de Ligação ao GTPRESUMO
Cholangiocarcinoma is a rare tumor but a challenging cancer in terms of pathological changes, clinical manifestations and therapeutic options. Recent studies have provided evidence for participation of non-coding RNAs in the carcinogenic process of cholangiocarcinoma. We demonstrate the role of long non-coding RNAs, microRNAs and circular RNAs in the pathogenesis of cholangiocarcinoma and highlight their significant position as therapeutic targets and biomarkers for this type of cancer. We also list a number of molecular axes comprising these non-coding RNAs that represent potential targets for therapeutic options in cholangiocarcinoma, based on their significant roles in the regulation of cell proliferation, differentiation and apoptosis of these cells.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , MicroRNAs , RNA Longo não Codificante , Humanos , RNA não Traduzido/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Colangiocarcinoma/genética , Ductos Biliares Intra-Hepáticos , Neoplasias dos Ductos Biliares/genéticaRESUMO
The construction of a competing endogenous RNA (ceRNA) network is an important step in the identification of the role of differentially expressed genes in cancers. In the current research, we used a number of bioinformatics tools to construct the ceRNA network in prostate cancer and identify the importance of these modules in predicting the survival of patients with this type of cancer. An assessment of microarray data of prostate cancer and normal samples using the Limma package led to the identification of differential expressed (DE) RNAs that we stratified into mRNA, lncRNA, and miRNAs, resulting in 684 DEmRNAs, including 437 downregulated DEmRNAs (such as TGM4 and SCGB1A1) and 241 upregulated DEmRNAs (such as TDRD1 and CRISP3); 6 DElncRNAs, including 1 downregulated DElncRNA (H19) and 5 upregulated DElncRNAs (such as PCA3 and PCGEM1); and 59 DEmiRNAs, including 30 downregulated DEmiRNAs (such as hsa-miR-1274a and hsa-miR-1274b) and 29 upregulated DEmiRNAs (such as hsa-miR-1268 and hsa-miR-1207-5p). The ceRNA network contained a total of 5 miRNAs, 5 lncRNAs, and 17 mRNAs. We identified hsa-miR-17, hsa-miR-93, hsa-miR-150, hsa-miR-25, PART1, hsa-miR-125b, PCA3, H19, RND3, and ITGB8 as the 10 hub genes in the ceRNA network. According to the ROC analysis, the expression levels of 19 hub genes showed a high diagnostic value. Taken together, we introduce a number of novel promising diagnostic biomarkers for prostate cancer.
Assuntos
MicroRNAs , Neoplasias da Próstata , RNA Longo não Codificante , Masculino , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , Redes Reguladoras de Genes , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genéticaRESUMO
Long intergenic non-protein coding RNA 324 (LINC00324) is an example of lncRNAs whose roles in the carcinogenesis is being elucidated. This lncRNA is encoded by a gene located on 17p13.1. It has been shown to be over-expressed in a variety of cancer cell lines and tumoral tissues. However, there are few reports showing down-regulation of LINC00324 in cancer cell lines and tissues. miR-615-5p/AKT1, miR-139-5p/IGF1R, miR-769-5p/STAT3, miR-3200-5p/BCAT1 and miR-214-5p/CDK6/CCND1/MDM2/MDM4 are examples of miRNA/mRNA axes being influenced by LINC00324. LINC00324 can be regarded as a promising candidate for development of diagnostic and prognostic panels. Moreover, it can be used a therapeutic target for a wide range of cancers. The current review summarizes the evidence regarding the impact of lINC00324 in the carcinogenic processes.
Assuntos
MicroRNAs , Neoplasias , RNA Longo não Codificante , Humanos , Neoplasias/genética , Carcinogênese , RNA Longo não Codificante/genética , Carcinógenos , Proteínas Proto-Oncogênicas , Proteínas de Ciclo Celular , TransaminasesRESUMO
Atraric acid (AA) is a natural compound used for treatment of benign prostate hyperplasia. This agent has an anti-androgen receptor (AR) activity suppressing androgen-mediated neo-angiogenesis. In the current study, we have analyzed the transcriptome data of prostate cancer cells treated with AA (GSE172205) to find differentially expressed genes (DEGs) with an especial focus on lncRNAs and miRNAs. Then, we assessed expression of the differentially expressed lncRNAs (DElncRNAs) in available online sources to validate their association with prostate cancer and their importance in the determination of survival of patients with this type of cancer. We obtained 1871 DEGs, including 914 down-regulated DEGs (such as DAB1 and CD200) and 957 up-regulated DEGs (such as CHRNA2 and TRGC1), and 25 DElncRNAs, including 15 down-regulated DElncRNAs (such as LINC00639 and HOTTIP) and 10 up-regulated DElncRNAs (such as LINC00844 and LINC00160), and one up-regulated DEmiRNA (MIR29B1). The main pathways for the down-regulated genes and the up-regulated genes were Axon Guidance and Steroid BioSynthesis, respectively. Taken together, AA has been found to affect expression of several lncRNAs which are possibly involved in the pathoetiology of prostate cancer.
Assuntos
Neoplasias de Próstata Resistentes à Castração , RNA Longo não Codificante , Masculino , Humanos , RNA Longo não Codificante/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Hidroxibenzoatos , Análise de Sequência de RNARESUMO
Autophagy has an established role in the development and progression of breast cancer. Recent studies have shown functional links between long non-coding RNAs (lncRNAs) and autophagy process. LINC01963, AL132989.1, RAB11B-AS1, PLBD1-AS1, AL139158.2, LOC105376805 (BX284668.5) and HERPUD2-AS1 (AC018647.2) are among autophagy related lncRNAs. In the current study, we compared expression of these seven lncRNAs between breast cancer samples and their paired non-cancerous tissues. RAB11B-AS1, HERPUD2-AS1 and PLBD1-AS1 were up-regulated in tumor samples compared with non-tumoral samples (Expression ratios (95% CI) = 2.56 (1.22-5.36), 2.13 (1.02-4.43) and 21.3 (10.36-43.89), respectively). ROC curve analysis indicated that PLBD1-AS1, RAB11B-AS1 and HERPUD2-AS1 had AUC values of 0.78, 0.61 and 0.6 for separation of breast cancer tissues from controls. Expression level of AL132989.1 in tumor tissues was associated with tubule formation (P value=0.02) in a way that tumor tissues with tubular formation score 1 had lower expression of AL132989.1. There was also a significant difference between expression levels of AL139158.2.1 among tumor tissues with different clinical stages (P value=0.02). Tumor tissues with higher clinical stages showed decreased expression of AL139158.2.1. In addition, there was also a significant difference between expression level of HERPUD2-AS1 in tumor tissues with different histological tumor grade and tubule formation (P value=0.03 and 0.003, respectively). Tumor tissues with higher histological tumor grade and higher tubule formation score showed higher expression of HERPUD2-AS1. Taken together, this study provides evidence for contribution of a number of recently identified autophagy-related lncRNAs in the pathogenesis of breast cancer.
Assuntos
Neoplasias da Mama , RNA Longo não Codificante , Humanos , Feminino , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Irã (Geográfico) , Regulação Neoplásica da Expressão Gênica/genética , Autofagia/genéticaRESUMO
Glioblastoma multiforme (GBM) is the most frequent malignant type of primary brain cancers and is a malignancy with poor prognosis. Thus, it is necessary to find novel therapeutic modalities based on molecular events occur at different stages of tumor progression. We used expression profiles of GBM tissues that contained long non-coding RNA (lncRNA), microRNA (miRNA) and mRNA signatures to make putative ceRNA networks. Our strategy led to identification of 1080 DEmRNAs, including 777 downregulated DEmRNAs (such as GJB6 and SLC12A5) and 303 upregulated DEmRNAs (such as TOP2A and RRM2), 19 DElncRNAs, including 16 downregulated DElncRNAs (such as MIR7-3HG and MIR124-2HG) and 3 upregulated DElncRNAs (such as CRNDE and XIST) and 49 DEmiRNAs, including 10 downregulated DEmiRNAs (such as hsa-miR-10b-5p and hsa-miR-1290) and 39 upregulated DEmiRNAs (such as hsa-miR-219a-2-3p and hsa-miR-338-5p). We also identified DGCR5, MIAT, hsa-miR-129-5p, XIST, hsa-miR-128-3p, PART1, hsa-miR-10b-5p, LY86-AS1, CRNDE, and DLX6-AS1 as 10 hub genes in the ceRNA network. The current study provides novel insight into molecular events during GBM pathogenesis. The identified molecules can be used as therapeutic targets for GBM.
RESUMO
Non-functioning pituitary adenoma (NFPA) is a benign tumor arising from the adenohypophyseal cells. They can be associated with symptoms arising from mass effect. Although these tumors are regarded to be benign tumors, they are associated with increased comorbidity and mortality. Several studies have indicated abnormal expression of genes in these tumors. In the current study, we have used existing methods to identify differentially expressed genes (DEGs) including DE long non-coding RNAs (DElncRNAs) and DE microRNAs (DEmiRNAs) in NFPAs compared with normal samples. Then, we have assessed the relation between these genes and important signaling pathways. Our analyses led to identification of 3131 DEGs, including 189 downregulated DEGs (such as RPS4Y1 and DDX3Y) and 2898 upregulated DEGs (such as ASB3 and DRD4), and 44 DElncRNAs, including 8 downregulated DElncRNAs (such as NUTM2B-AS1 and MALAT1) and 36 upregulated DElncRNAs (such as BCAR4 and SRD5A3-AS1). GnRH signaling pathway, Tight junction, Gap junction, Melanogenesis, DNA replication, Nucleotide excision repair, Mismatch repair and N-Glycan biosynthesis have been among dysregulated pathways in NFPAs. Taken together, our study has revealed differential expression of several genes and signaling pathways in this type of tumors.