Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA219064 | ENA |
REPOSITORIES: ENA
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Project description:Anchorage of tissue cells to their physical environment is an obligate requirement for survival that is lost in mature hematopoietic and in transformed epithelial cells. Here we find that a lymphocyte lineage-restricted transcription factor, Aiolos, is frequently expressed in lung cancers and predicts markedly reduced patient survival. Aiolos decreases expression of a large set of adhesion-related genes, disrupting cell-cell and cell-matrix interactions. Aiolos also reconfigures chromatin structure within the SHC1 gene, causing isoform-specific silencing of the anchorage reporter p66Shc and blocking anoikis in vitro and in vivo. In lung cancer tissues and single cells, p66Shc expression inversely correlates with that of Aiolos. Together, these findings suggest that Aiolos functions as an epigenetic driver of lymphocyte mimicry in metastatic epithelial cancers.
2013-09-13 | GSE50812 | GEO
Project description:Analysis of transcriptional profiling change comparing A549 cells expressing control empty vector and A549 cells expressing Aiolos. Results provide insight into molecular mechanisms underlying functional consequence of ectopic expression of Aiolos in solid cancer cells. Two-condition experiment, A549-empty vs. A549-Aiolos cells. Biological replicates: 3 control, 3 transfected, independently grown and harvested. One replicate per array.
2013-09-13 | E-GEOD-50812 | biostudies-arrayexpress
Project description:Aberrant methylation-mediated silencing of microRNAs contributes to HPV-induced anchorage independence
| PRJNA313079 | ENA
Project description:Background: JAG-1 is a ligand of Notch signaling and can regulate cell differentiation and proliferation in cancers. Recent studies indicated that JAG1 is a gene associated with cancer progression. Therefore, we investigated the role of JAG1 in lung cancer progression. Methods: The expression of JAG1 was manipulated by overexpression or RNA silencing in several human lung cell lines. The effect of JAG1 on tumorigenesis and invasion was assessed by the cell anchorage-independent growth, cell proliferation, cell migration and invasion assays in vitro as well as metastasis in vivo. The potential downstream genes of JAG1 were identified by oligonucleotide microarrays and quantitative reverse transcription¡Vpolymerase chain reaction (RT-PCR). We further measured JAG1 expression in lung cancer specimens by RT-PCR. Correlation between JAG1 expression and overall survival of lung cancer patients was determined by using the log-rank test and multivariable Cox proportional hazards regression analysis. All statistical tests were two-sided. Results: JAG1 enhanced anchorage-independent growth, cell migration, invasion in the lower invasive cells, CL1-0. JAG1 also increased the capability of migration and invasion in the other two lung cancer cell lines (A549 and NCI-H226). The silencing of JAG1 inhibited migration and invasion activities of the higher invasive cells, CL1-5, by siRNA technology. The invasion-promoting activity of JAG1 was also demonstrated in vivo by using a mouse metastasis model. By microarray analysis, we found that the expression of heat shock 70kDa protein 2 (HSPA2) was activated by JAG1 overexpression and eliminated by JAG1 silencing. Moreover, lung cancer patients with high JAG1 expressing tumors had shorter overall survival than those with low-expressing tumors. Conclusion: JAG1 might be an oncogene which promotes colonogenesis and metastasis, and high JAG1 expression is associated with shorten survival in lung cancer.
2013-01-12 | GSE14995 | GEO
Project description:Cervical cancer and a subset of anogenital and head-and-neck carcinomas are caused by persistent infection with high-risk types of the human papillomavirus (hrHPV). Early stages of hrHPV-induced carcinogenesis can be faithfully mimicked in vitro. A major hallmark of hrHPV-transformed cells is their ability to grow anchorage independently, an oncogenic trait known to depend on inactivation of tumour suppressor genes. This study used an in vitro model of hrHPV-induced transformation to delineate in a longitudinal manner to what extent DNA methylation-mediated silencing of tumour suppressive microRNAs (miRNAs) contributed to hrHPV-induced anchorage independence. Genome-wide miRNA expression profiles were yielded from anchorage dependent (n=11) and independent passages (n=19) of 4 hrHPV-immortalised keratinocyte cell lines with and without demethylating treatment (DAC). Unsupervised clustering analysis showed that overall miRNA expression patterns discriminated between anchorage dependent and independent cells. Ten miRNA genes potentially silenced by methylation were selected and validated by bisulfite sequencing and methylation-specific PCR. Hsa-mir-129-2, -137, -935, -3663, -3665, and -4281 showed increased methylation in both HPV-transformed keratinocytes and cervical cancer cell lines compared to primary keratinocytes. Mature miRNAs derived from hsa-mir-129-2, -137, -3663, and -3665 decreased anchorage independence in cervical cancer cell lines. Finally, significantly increased methylation of hsa-mir-129-2, -935, -3663, -3665, and -4281 was observed in cervical (pre)cancerous lesions, underlining the clinical relevance of our findings. In conclusion, methylation-mediated silencing of tumour suppressive miRNAs contributes to the acquisition of anchorage independence, supporting the importance of miRNAs during early stages of carcinogenesis and underlining their potential as both disease markers and therapeutic targets.
2017-02-09 | GSE78278 | GEO
Project description:Cervical cancer and a subset of anogenital and head-and-neck carcinomas are caused by persistent infection with high-risk types of the human papillomavirus (hrHPV). Early stages of hrHPV-induced carcinogenesis can be faithfully mimicked in vitro. A major hallmark of hrHPV-transformed cells is their ability to grow anchorage independently, an oncogenic trait known to depend on inactivation of tumour suppressor genes. This study used an in vitro model of hrHPV-induced transformation to delineate in a longitudinal manner to what extent DNA methylation-mediated silencing of tumour suppressive microRNAs (miRNAs) contributed to hrHPV-induced anchorage independence. Genome-wide miRNA expression profiles were yielded from anchorage dependent (n=11) and independent passages (n=19) of 4 hrHPV-immortalised keratinocyte cell lines with and without demethylating treatment (DAC). Unsupervised clustering analysis showed that overall miRNA expression patterns discriminated between anchorage dependent and independent cells. Ten miRNA genes potentially silenced by methylation were selected and validated by bisulfite sequencing and methylation-specific PCR. Hsa-mir-129-2, -137, -935, -3663, -3665, and -4281 showed increased methylation in both HPV-transformed keratinocytes and cervical cancer cell lines compared to primary keratinocytes. Mature miRNAs derived from hsa-mir-129-2, -137, -3663, and -3665 decreased anchorage independence in cervical cancer cell lines. Finally, significantly increased methylation of hsa-mir-129-2, -935, -3663, -3665, and -4281 was observed in cervical (pre)cancerous lesions, underlining the clinical relevance of our findings. In conclusion, methylation-mediated silencing of tumour suppressive miRNAs contributes to the acquisition of anchorage independence, supporting the importance of miRNAs during early stages of carcinogenesis and underlining their potential as both disease markers and therapeutic targets.
2017-02-09 | GSE78277 | GEO
Project description:Background: JAG-1 is a ligand of Notch signaling and can regulate cell differentiation and proliferation in cancers. Recent studies indicated that JAG1 is a gene associated with cancer progression. Therefore, we investigated the role of JAG1 in lung cancer progression. Methods: The expression of JAG1 was manipulated by overexpression or RNA silencing in several human lung cell lines. The effect of JAG1 on tumorigenesis and invasion was assessed by the cell anchorage-independent growth, cell proliferation, cell migration and invasion assays in vitro as well as metastasis in vivo. The potential downstream genes of JAG1 were identified by oligonucleotide microarrays and quantitative reverse transcription¡Vpolymerase chain reaction (RT-PCR). We further measured JAG1 expression in lung cancer specimens by RT-PCR. Correlation between JAG1 expression and overall survival of lung cancer patients was determined by using the log-rank test and multivariable Cox proportional hazards regression analysis. All statistical tests were two-sided. Results: JAG1 enhanced anchorage-independent growth, cell migration, invasion in the lower invasive cells, CL1-0. JAG1 also increased the capability of migration and invasion in the other two lung cancer cell lines (A549 and NCI-H226). The silencing of JAG1 inhibited migration and invasion activities of the higher invasive cells, CL1-5, by siRNA technology. The invasion-promoting activity of JAG1 was also demonstrated in vivo by using a mouse metastasis model. By microarray analysis, we found that the expression of heat shock 70kDa protein 2 (HSPA2) was activated by JAG1 overexpression and eliminated by JAG1 silencing. Moreover, lung cancer patients with high JAG1 expressing tumors had shorter overall survival than those with low-expressing tumors. Conclusion: JAG1 might be an oncogene which promotes colonogenesis and metastasis, and high JAG1 expression is associated with shorten survival in lung cancer. In this investigation, we used a lung cancer invasion cell model to identify the genes involved in cancer progression. JAG1 is a potential oncogene whose expression is correlated to the survival of patients with breast, prostate and liver cancers. However, the role of JAG1 in lung caner progression has not been reported, particularly in metastasis. Here, JAG1 was ectopically expressed in lower invasive lung cancer cell line its impact on colonogenesis, migration and invasiveness was assessed. The underlying mechanism was explored by JAG1-expressed transfectants and microarrays and the clinical relevance was evaluated by quantitative RT-PCR.
2013-01-12 | E-GEOD-14995 | biostudies-arrayexpress
Project description:Recent studies demonstrated that cancer stem cells (CSCs) have higher tumorigenesis properties than those of differentiated cancer cells and that transcriptional factor-SOX2 plays a vital role in maintaining the unique properties of CSCs; however, the function and underlying mechanism of SOX2 in carcinogenesis of lung cancer are still elusive. This study applied immunohistochemistry to analyze the expression of SOX2 in human lung tissues of normal individuals as well as patients with adenocarcinoma, squamous cell carcinoma, large cell and small cell carcinoma and demonstrated specific overexpression of SOX2 in all types of lung cancer tissues. This finding supports the notion that SOX2 contributes to the tumorigenesis of lung cancer cells and can be used as a diagnostic probe. In addition, obviously higher expression of oncogenes c-MYC, WNT1, WNT2 and NOTCH1 was detected in side population (SP) cells than in none side population (NSP) cells of human lung adenocarcinoma cell line-A549, revealing a possible mechanism for the tenacious tumorigenic potential of CSCs. To further elucidate the function of SOX2 in tumorigenesis of cancer cells, A549 cells were established with expression of luciferase and doxycycline inducible shRNA targeting SOX2. We found silencing of SOX2 gene reduces the tumorigenic property of A549 cells with attenuated expression of c-MYC, WNT1, WNT2 and NOTCH1 in xenografted NOD/SCID mice. By RNA-Seq method, additional 246 target cancer genes of SOX2 were revealed. These results present evidence that SOX2 may regulate the expression of oncogenes in CSCs to promote the development of human lung cancer. Examination of mRNA profiles in A549 cells with SOX2 silencing
2012-08-31 | E-GEOD-36597 | biostudies-arrayexpress
Project description:Epigenetic regulators are attractive targets for the development of new cancer therapies. Among them, the ATP-dependent chromatin remodeling complexes control the chromatin architecture and play important roles in gene regulation. They are often found to be mutated and de-regulated in cancers, but how they influence the cancer gene expression program during cancer initiation and progression is not fully understood. Here we show that the INO80 chromatin remodeling complex is required for oncogenic transcription and tumor growth in non-small cell lung cancer (NSCLC). Ino80, the SWI/SNF ATPase in the complex, is highly expressed in NSCLC cells compared to normal lung epithelia cells. Further, its expression, as well as that of another subunit Ino80b, negatively correlates with disease prognosis in lung cancer patients. Functionally, Ino80 silencing inhibits NSCLC cell proliferation and anchorage-independent growth in vitro and tumor formation in mouse xenografts. It occupies enhancer regions near lung cancer-associated genes, and its occupancy correlates with increased genome accessibility and enhanced expression of downstream genes. Together, our study defines a critical role of INO80 in promoting oncogenic transcription and NSCLC tumorigenesis, and reveals a potential treatment strategy for inhibiting the cancer transcription network by targeting the INO80 chromatin remodeling complex. Human lung cancer cell line A549 cells were infected with shNT or shIno80, and total RNA was extracted 4 days after infection. The RNA was submitted to RNA-Seq subsequently. For ChIP-Seq, A549 infected with shNT or shIno80, was used for ChIP-Seq for corresponding factors.
2016-08-03 | E-GEOD-85118 | biostudies-arrayexpress