The Experts below are selected from a list of 336948 Experts worldwide ranked by ideXlab platform

Jay S Wunder - One of the best experts on this subject based on the ideXlab platform.

  • abstract lb 306 long non coding rna neat1 promotes lung Metastasis of soft tissue sarcoma by regulating rna splicing pathways
    Cancer Research, 2019
    Co-Authors: Jianguo Huang, Eric S Xu, Mohit Sachdeva, Timothy J Robinson, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene L Andrulis, Jay S Wunder
    Abstract:

    Soft tissue sarcomas (STS) are malignant tumors from diverse mesenchymal tissues. About 40% STS patients develop fatal lung Metastasis with a median survival of 15 months. The mechanisms driving the development of lung Metastasis in sarcoma patients are poorly understood. Therefore, our lab has developed a genetically engineered mouse model (GEMM) of high-grade primary STS with conditional mutations in Kras and Trp53 (KP) where 40% of mice tumors develop lung Metastasis. This KP model recapitulates human patients with Undifferentiated Pleomorphic Sarcoma (UPS), one of the most common subtypes of STS diagnosed in adults. RNA sequencing (RNA-Seq) was performed on paired primary and lung metastases in KP mouse sarcomas and determined that the expression of the long non-coding RNA (lncRNA) Neat1 is increased in lung metastases compared to paired primary tumors. Real time PCR (qPCR) in 22 paired KP mouse primary sarcomas and lung metastases further confirmed that Neat1 is significantly upregulated in some lung metastases. In addition, RNA-Seq and qPCR data from 10 pairs of human primary sarcomas and matched lung metastases also showed that NEAT1 levels are increased in lung metastases. Furthermore, NEAT1 RNA in situ hybridization (ISH) on tissue microarrays (TMAs) of human primary UPS and lung metastases determined that the expression of NEAT1 is upregulated in lung metastases. Next, CRISPR/Cas9 technology was applied to delete Neat1 in primary mouse sarcoma cells and loss of expression of Neat1 was confirmed by qPCR and northern blot in knockout (KO) clones. In addition, loss of Neat1 significantly reduced lung Metastasis in vivo following tail vein injection of these modified cells into nude mice. Furthermore, RNA pull down assay with mass spectrometry analysis determined Neat1 interacting proteins, such as Khsrp, were mainly involved in RNA splicing pathways which was also shown to be dysregulated in lung metastases and Neat1 KO cells. Finally, CRISPR/Cas9 mediated knockout of Khsrp significantly reduced lung Metastasis in vivo following tail vein injection of these modified cells into nude mice. Overall, these results suggest that upregulation of Neat1 promotes lung Metastasis of soft tissue sarcoma through regulating RNA splicing pathways and NEAT1 is a potential target to prevent or treat lung Metastasis in sarcoma patients. Citation Format: Jianguo Huang, Eric Xu, Mohit Sachdeva, Timothy Robinson, Xiaodi Qin, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene Andrulis, Jay Wunder, Tomoyo Okada, Simuel Singer, Alexander Lazar, Brian Rubin, David G. Kirsch. Long non-coding RNA NEAT1 promotes lung Metastasis of soft tissue sarcoma by regulating RNA splicing pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-306.

  • abstract 516 long noncoding rna neat1 promotes lung Metastasis of soft tissue sarcoma
    Cancer Research, 2018
    Co-Authors: Jianguo Huang, Eric S Xu, Mohit Sachdeva, Timothy J Robinson, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene L Andrulis, Jay S Wunder
    Abstract:

    Soft tissue sarcomas (STS) are malignant tumors from diverse mesenchymal tissues. About 40% STS patients develop fatal lung Metastasis with a median survival of 15 months. The mechanisms driving the development of lung Metastasis in sarcoma patients are poorly understood. Therefore, our lab has developed a genetically engineered mouse model (GEMM) of high-grade primary STS with conditional mutations in Kras and Trp53 (KP) where 40% of mice tumors develop lung Metastasis. This KP model recapitulates human patients with Undifferentiated Pleomorphic Sarcoma (UPS), one of the most common subtypes of STS diagnosed in adults. RNA sequencing (RNA-Seq) was performed on paired primary and lung metastases in KP mouse sarcomas and determined that the expression of the long non-coding RNA (lncRNA) Neat1 is increased in lung metastases compared to paired primary tumors. Real time PCR (qPCR) in 22 paired KP mouse primary sarcomas and lung metastases further confirmed that Neat1 is significantly upregulated in lung metastases. In addition, RNA-Seq data from 5 pairs of human primary sarcomas and matched lung metastases also showed that NEAT1 levels are increased in lung metastases. Furthermore, NEAT1 RNA in situ hybridization (ISH) on tissue microarrays (TMAs) of human primary UPS and lung metastases determined that the expression of NEAT1 is upregulated in lung metastases. Next, CRISPR/Cas9 technology was applied to delete Neat1 in primary mouse sarcoma cells and loss of expression of Neat1 was confirmed by qPCR and northern blot in knockout (KO) clones. In addition, loss of Neat1 significantly reduced lung Metastasis in vivo following tail vein injection of these modified cells into nude mice. To further test that loss of Neat1 reduces lung Metastasis in primary sarcoma mouse model, primary tumors with Neat1 deletion are generated in GEMMs using in vivo CRISPR/Cas9 technology and KrasLSL-G12D/+; Trp53Flox/Flox; Neat1-/- (KPN) mouse model. Finally, RNA-Seq and capture hybridization analysis of RNA targets (CHART) are performed to determine mechanisms by which Neat1 regulates lung Metastasis. Overall, these results suggest that upregulation of Neat1 promotes lung Metastasis of soft tissue sarcoma and NEAT1 is a potential target to prevent or treat lung Metastasis in sarcoma patients. Citation Format: Jianguo Huang, Eric Xu, Mohit Sachdeva, Timothy Robinson, Xiaodi Qin, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene Andrulis, Jay Wunder, Tomoyo Okada, Samuel Singer, Alexander Lazar, Brian Rubin, David G. Kirsch. Long noncoding RNA NEAT1 promotes lung Metastasis of soft tissue sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 516.

Jianguo Huang - One of the best experts on this subject based on the ideXlab platform.

  • abstract lb 306 long non coding rna neat1 promotes lung Metastasis of soft tissue sarcoma by regulating rna splicing pathways
    Cancer Research, 2019
    Co-Authors: Jianguo Huang, Eric S Xu, Mohit Sachdeva, Timothy J Robinson, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene L Andrulis, Jay S Wunder
    Abstract:

    Soft tissue sarcomas (STS) are malignant tumors from diverse mesenchymal tissues. About 40% STS patients develop fatal lung Metastasis with a median survival of 15 months. The mechanisms driving the development of lung Metastasis in sarcoma patients are poorly understood. Therefore, our lab has developed a genetically engineered mouse model (GEMM) of high-grade primary STS with conditional mutations in Kras and Trp53 (KP) where 40% of mice tumors develop lung Metastasis. This KP model recapitulates human patients with Undifferentiated Pleomorphic Sarcoma (UPS), one of the most common subtypes of STS diagnosed in adults. RNA sequencing (RNA-Seq) was performed on paired primary and lung metastases in KP mouse sarcomas and determined that the expression of the long non-coding RNA (lncRNA) Neat1 is increased in lung metastases compared to paired primary tumors. Real time PCR (qPCR) in 22 paired KP mouse primary sarcomas and lung metastases further confirmed that Neat1 is significantly upregulated in some lung metastases. In addition, RNA-Seq and qPCR data from 10 pairs of human primary sarcomas and matched lung metastases also showed that NEAT1 levels are increased in lung metastases. Furthermore, NEAT1 RNA in situ hybridization (ISH) on tissue microarrays (TMAs) of human primary UPS and lung metastases determined that the expression of NEAT1 is upregulated in lung metastases. Next, CRISPR/Cas9 technology was applied to delete Neat1 in primary mouse sarcoma cells and loss of expression of Neat1 was confirmed by qPCR and northern blot in knockout (KO) clones. In addition, loss of Neat1 significantly reduced lung Metastasis in vivo following tail vein injection of these modified cells into nude mice. Furthermore, RNA pull down assay with mass spectrometry analysis determined Neat1 interacting proteins, such as Khsrp, were mainly involved in RNA splicing pathways which was also shown to be dysregulated in lung metastases and Neat1 KO cells. Finally, CRISPR/Cas9 mediated knockout of Khsrp significantly reduced lung Metastasis in vivo following tail vein injection of these modified cells into nude mice. Overall, these results suggest that upregulation of Neat1 promotes lung Metastasis of soft tissue sarcoma through regulating RNA splicing pathways and NEAT1 is a potential target to prevent or treat lung Metastasis in sarcoma patients. Citation Format: Jianguo Huang, Eric Xu, Mohit Sachdeva, Timothy Robinson, Xiaodi Qin, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene Andrulis, Jay Wunder, Tomoyo Okada, Simuel Singer, Alexander Lazar, Brian Rubin, David G. Kirsch. Long non-coding RNA NEAT1 promotes lung Metastasis of soft tissue sarcoma by regulating RNA splicing pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-306.

  • abstract 516 long noncoding rna neat1 promotes lung Metastasis of soft tissue sarcoma
    Cancer Research, 2018
    Co-Authors: Jianguo Huang, Eric S Xu, Mohit Sachdeva, Timothy J Robinson, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene L Andrulis, Jay S Wunder
    Abstract:

    Soft tissue sarcomas (STS) are malignant tumors from diverse mesenchymal tissues. About 40% STS patients develop fatal lung Metastasis with a median survival of 15 months. The mechanisms driving the development of lung Metastasis in sarcoma patients are poorly understood. Therefore, our lab has developed a genetically engineered mouse model (GEMM) of high-grade primary STS with conditional mutations in Kras and Trp53 (KP) where 40% of mice tumors develop lung Metastasis. This KP model recapitulates human patients with Undifferentiated Pleomorphic Sarcoma (UPS), one of the most common subtypes of STS diagnosed in adults. RNA sequencing (RNA-Seq) was performed on paired primary and lung metastases in KP mouse sarcomas and determined that the expression of the long non-coding RNA (lncRNA) Neat1 is increased in lung metastases compared to paired primary tumors. Real time PCR (qPCR) in 22 paired KP mouse primary sarcomas and lung metastases further confirmed that Neat1 is significantly upregulated in lung metastases. In addition, RNA-Seq data from 5 pairs of human primary sarcomas and matched lung metastases also showed that NEAT1 levels are increased in lung metastases. Furthermore, NEAT1 RNA in situ hybridization (ISH) on tissue microarrays (TMAs) of human primary UPS and lung metastases determined that the expression of NEAT1 is upregulated in lung metastases. Next, CRISPR/Cas9 technology was applied to delete Neat1 in primary mouse sarcoma cells and loss of expression of Neat1 was confirmed by qPCR and northern blot in knockout (KO) clones. In addition, loss of Neat1 significantly reduced lung Metastasis in vivo following tail vein injection of these modified cells into nude mice. To further test that loss of Neat1 reduces lung Metastasis in primary sarcoma mouse model, primary tumors with Neat1 deletion are generated in GEMMs using in vivo CRISPR/Cas9 technology and KrasLSL-G12D/+; Trp53Flox/Flox; Neat1-/- (KPN) mouse model. Finally, RNA-Seq and capture hybridization analysis of RNA targets (CHART) are performed to determine mechanisms by which Neat1 regulates lung Metastasis. Overall, these results suggest that upregulation of Neat1 promotes lung Metastasis of soft tissue sarcoma and NEAT1 is a potential target to prevent or treat lung Metastasis in sarcoma patients. Citation Format: Jianguo Huang, Eric Xu, Mohit Sachdeva, Timothy Robinson, Xiaodi Qin, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene Andrulis, Jay Wunder, Tomoyo Okada, Samuel Singer, Alexander Lazar, Brian Rubin, David G. Kirsch. Long noncoding RNA NEAT1 promotes lung Metastasis of soft tissue sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 516.

Peter T Dziegielewski - One of the best experts on this subject based on the ideXlab platform.

  • follicular thyroid carcinoma Metastasis to the facial skeleton a systematic review
    BMC Cancer, 2017
    Co-Authors: Varun V Varadarajan, Elizabeth Pace, Vatsal Patel, Raja Sawhney, Robert J Amdur, Peter T Dziegielewski
    Abstract:

    Follicular thyroid carcinoma (FTC) Metastasis to the facial skeleton is exceedingly rare. A case of FTC metastasizing to the mandible is presented and a systematic review of the literature describing thyroid Metastasis to the facial skeleton is performed. A 73-year-old female presented with metastatic FTC to the mandible and underwent total thyroidectomy, segmental mandibulectomy, bone impacted fibular free flap reconstruction, and adjuvant radioactive iodine treatment. The PubMed database was searched for literature describing thyroid cancer with facial skeleton Metastasis using the key words “thyroid,” “cancer,” “carcinoma,” “Metastasis,” and “malignancy” with “oral cavity,” “maxilla,” “mandible,” “sinus,” “paranasal,” and “orbit.” Reports that only involved the soft tissues were excluded. Systematic review revealed 59 cases of well-differentiated thyroid cancer with facial skeleton Metastasis: 35 mandibular metastases (21 = FTC), 6 maxilla metastases (2 = FTC), 9 orbital metastases (4 = FTC), and 11 paranasal sinus metastases (7 = FTC). Treatment included surgery, RAI, external beam radiotherapy (XRT), or a combination of these modalities. The one, two, and five-year survival rates were 100%, 79%, and 16%, respectively. Facial skeleton Metastasis of FTC is a rare clinical challenge. Optimal treatment appears to include total thyroidectomy and resection of involved structures with or without adjuvant treatment.

  • Follicular thyroid carcinoma Metastasis to the facial skeleton: a systematic review
    BMC Cancer, 2017
    Co-Authors: Varun V Varadarajan, Vatsal Patel, Raja Sawhney, Robert J Amdur, Elizabeth K. Pace, Peter T Dziegielewski
    Abstract:

    Background Follicular thyroid carcinoma (FTC) Metastasis to the facial skeleton is exceedingly rare. A case of FTC metastasizing to the mandible is presented and a systematic review of the literature describing thyroid Metastasis to the facial skeleton is performed. Case presentation A 73-year-old female presented with metastatic FTC to the mandible and underwent total thyroidectomy, segmental mandibulectomy, bone impacted fibular free flap reconstruction, and adjuvant radioactive iodine treatment. The PubMed database was searched for literature describing thyroid cancer with facial skeleton Metastasis using the key words “thyroid,” “cancer,” “carcinoma,” “Metastasis,” and “malignancy” with “oral cavity,” “maxilla,” “mandible,” “sinus,” “paranasal,” and “orbit.” Reports that only involved the soft tissues were excluded. Systematic review revealed 59 cases of well-differentiated thyroid cancer with facial skeleton Metastasis: 35 mandibular metastases (21 = FTC), 6 maxilla metastases (2 = FTC), 9 orbital metastases (4 = FTC), and 11 paranasal sinus metastases (7 = FTC). Treatment included surgery, RAI, external beam radiotherapy (XRT), or a combination of these modalities. The one, two, and five-year survival rates were 100%, 79%, and 16%, respectively. Conclusion Facial skeleton Metastasis of FTC is a rare clinical challenge. Optimal treatment appears to include total thyroidectomy and resection of involved structures with or without adjuvant treatment.

Timothy J Robinson - One of the best experts on this subject based on the ideXlab platform.

  • abstract lb 306 long non coding rna neat1 promotes lung Metastasis of soft tissue sarcoma by regulating rna splicing pathways
    Cancer Research, 2019
    Co-Authors: Jianguo Huang, Eric S Xu, Mohit Sachdeva, Timothy J Robinson, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene L Andrulis, Jay S Wunder
    Abstract:

    Soft tissue sarcomas (STS) are malignant tumors from diverse mesenchymal tissues. About 40% STS patients develop fatal lung Metastasis with a median survival of 15 months. The mechanisms driving the development of lung Metastasis in sarcoma patients are poorly understood. Therefore, our lab has developed a genetically engineered mouse model (GEMM) of high-grade primary STS with conditional mutations in Kras and Trp53 (KP) where 40% of mice tumors develop lung Metastasis. This KP model recapitulates human patients with Undifferentiated Pleomorphic Sarcoma (UPS), one of the most common subtypes of STS diagnosed in adults. RNA sequencing (RNA-Seq) was performed on paired primary and lung metastases in KP mouse sarcomas and determined that the expression of the long non-coding RNA (lncRNA) Neat1 is increased in lung metastases compared to paired primary tumors. Real time PCR (qPCR) in 22 paired KP mouse primary sarcomas and lung metastases further confirmed that Neat1 is significantly upregulated in some lung metastases. In addition, RNA-Seq and qPCR data from 10 pairs of human primary sarcomas and matched lung metastases also showed that NEAT1 levels are increased in lung metastases. Furthermore, NEAT1 RNA in situ hybridization (ISH) on tissue microarrays (TMAs) of human primary UPS and lung metastases determined that the expression of NEAT1 is upregulated in lung metastases. Next, CRISPR/Cas9 technology was applied to delete Neat1 in primary mouse sarcoma cells and loss of expression of Neat1 was confirmed by qPCR and northern blot in knockout (KO) clones. In addition, loss of Neat1 significantly reduced lung Metastasis in vivo following tail vein injection of these modified cells into nude mice. Furthermore, RNA pull down assay with mass spectrometry analysis determined Neat1 interacting proteins, such as Khsrp, were mainly involved in RNA splicing pathways which was also shown to be dysregulated in lung metastases and Neat1 KO cells. Finally, CRISPR/Cas9 mediated knockout of Khsrp significantly reduced lung Metastasis in vivo following tail vein injection of these modified cells into nude mice. Overall, these results suggest that upregulation of Neat1 promotes lung Metastasis of soft tissue sarcoma through regulating RNA splicing pathways and NEAT1 is a potential target to prevent or treat lung Metastasis in sarcoma patients. Citation Format: Jianguo Huang, Eric Xu, Mohit Sachdeva, Timothy Robinson, Xiaodi Qin, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene Andrulis, Jay Wunder, Tomoyo Okada, Simuel Singer, Alexander Lazar, Brian Rubin, David G. Kirsch. Long non-coding RNA NEAT1 promotes lung Metastasis of soft tissue sarcoma by regulating RNA splicing pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-306.

  • abstract 516 long noncoding rna neat1 promotes lung Metastasis of soft tissue sarcoma
    Cancer Research, 2018
    Co-Authors: Jianguo Huang, Eric S Xu, Mohit Sachdeva, Timothy J Robinson, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene L Andrulis, Jay S Wunder
    Abstract:

    Soft tissue sarcomas (STS) are malignant tumors from diverse mesenchymal tissues. About 40% STS patients develop fatal lung Metastasis with a median survival of 15 months. The mechanisms driving the development of lung Metastasis in sarcoma patients are poorly understood. Therefore, our lab has developed a genetically engineered mouse model (GEMM) of high-grade primary STS with conditional mutations in Kras and Trp53 (KP) where 40% of mice tumors develop lung Metastasis. This KP model recapitulates human patients with Undifferentiated Pleomorphic Sarcoma (UPS), one of the most common subtypes of STS diagnosed in adults. RNA sequencing (RNA-Seq) was performed on paired primary and lung metastases in KP mouse sarcomas and determined that the expression of the long non-coding RNA (lncRNA) Neat1 is increased in lung metastases compared to paired primary tumors. Real time PCR (qPCR) in 22 paired KP mouse primary sarcomas and lung metastases further confirmed that Neat1 is significantly upregulated in lung metastases. In addition, RNA-Seq data from 5 pairs of human primary sarcomas and matched lung metastases also showed that NEAT1 levels are increased in lung metastases. Furthermore, NEAT1 RNA in situ hybridization (ISH) on tissue microarrays (TMAs) of human primary UPS and lung metastases determined that the expression of NEAT1 is upregulated in lung metastases. Next, CRISPR/Cas9 technology was applied to delete Neat1 in primary mouse sarcoma cells and loss of expression of Neat1 was confirmed by qPCR and northern blot in knockout (KO) clones. In addition, loss of Neat1 significantly reduced lung Metastasis in vivo following tail vein injection of these modified cells into nude mice. To further test that loss of Neat1 reduces lung Metastasis in primary sarcoma mouse model, primary tumors with Neat1 deletion are generated in GEMMs using in vivo CRISPR/Cas9 technology and KrasLSL-G12D/+; Trp53Flox/Flox; Neat1-/- (KPN) mouse model. Finally, RNA-Seq and capture hybridization analysis of RNA targets (CHART) are performed to determine mechanisms by which Neat1 regulates lung Metastasis. Overall, these results suggest that upregulation of Neat1 promotes lung Metastasis of soft tissue sarcoma and NEAT1 is a potential target to prevent or treat lung Metastasis in sarcoma patients. Citation Format: Jianguo Huang, Eric Xu, Mohit Sachdeva, Timothy Robinson, Xiaodi Qin, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene Andrulis, Jay Wunder, Tomoyo Okada, Samuel Singer, Alexander Lazar, Brian Rubin, David G. Kirsch. Long noncoding RNA NEAT1 promotes lung Metastasis of soft tissue sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 516.

Eric S Xu - One of the best experts on this subject based on the ideXlab platform.

  • abstract lb 306 long non coding rna neat1 promotes lung Metastasis of soft tissue sarcoma by regulating rna splicing pathways
    Cancer Research, 2019
    Co-Authors: Jianguo Huang, Eric S Xu, Mohit Sachdeva, Timothy J Robinson, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene L Andrulis, Jay S Wunder
    Abstract:

    Soft tissue sarcomas (STS) are malignant tumors from diverse mesenchymal tissues. About 40% STS patients develop fatal lung Metastasis with a median survival of 15 months. The mechanisms driving the development of lung Metastasis in sarcoma patients are poorly understood. Therefore, our lab has developed a genetically engineered mouse model (GEMM) of high-grade primary STS with conditional mutations in Kras and Trp53 (KP) where 40% of mice tumors develop lung Metastasis. This KP model recapitulates human patients with Undifferentiated Pleomorphic Sarcoma (UPS), one of the most common subtypes of STS diagnosed in adults. RNA sequencing (RNA-Seq) was performed on paired primary and lung metastases in KP mouse sarcomas and determined that the expression of the long non-coding RNA (lncRNA) Neat1 is increased in lung metastases compared to paired primary tumors. Real time PCR (qPCR) in 22 paired KP mouse primary sarcomas and lung metastases further confirmed that Neat1 is significantly upregulated in some lung metastases. In addition, RNA-Seq and qPCR data from 10 pairs of human primary sarcomas and matched lung metastases also showed that NEAT1 levels are increased in lung metastases. Furthermore, NEAT1 RNA in situ hybridization (ISH) on tissue microarrays (TMAs) of human primary UPS and lung metastases determined that the expression of NEAT1 is upregulated in lung metastases. Next, CRISPR/Cas9 technology was applied to delete Neat1 in primary mouse sarcoma cells and loss of expression of Neat1 was confirmed by qPCR and northern blot in knockout (KO) clones. In addition, loss of Neat1 significantly reduced lung Metastasis in vivo following tail vein injection of these modified cells into nude mice. Furthermore, RNA pull down assay with mass spectrometry analysis determined Neat1 interacting proteins, such as Khsrp, were mainly involved in RNA splicing pathways which was also shown to be dysregulated in lung metastases and Neat1 KO cells. Finally, CRISPR/Cas9 mediated knockout of Khsrp significantly reduced lung Metastasis in vivo following tail vein injection of these modified cells into nude mice. Overall, these results suggest that upregulation of Neat1 promotes lung Metastasis of soft tissue sarcoma through regulating RNA splicing pathways and NEAT1 is a potential target to prevent or treat lung Metastasis in sarcoma patients. Citation Format: Jianguo Huang, Eric Xu, Mohit Sachdeva, Timothy Robinson, Xiaodi Qin, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene Andrulis, Jay Wunder, Tomoyo Okada, Simuel Singer, Alexander Lazar, Brian Rubin, David G. Kirsch. Long non-coding RNA NEAT1 promotes lung Metastasis of soft tissue sarcoma by regulating RNA splicing pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-306.

  • abstract 516 long noncoding rna neat1 promotes lung Metastasis of soft tissue sarcoma
    Cancer Research, 2018
    Co-Authors: Jianguo Huang, Eric S Xu, Mohit Sachdeva, Timothy J Robinson, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene L Andrulis, Jay S Wunder
    Abstract:

    Soft tissue sarcomas (STS) are malignant tumors from diverse mesenchymal tissues. About 40% STS patients develop fatal lung Metastasis with a median survival of 15 months. The mechanisms driving the development of lung Metastasis in sarcoma patients are poorly understood. Therefore, our lab has developed a genetically engineered mouse model (GEMM) of high-grade primary STS with conditional mutations in Kras and Trp53 (KP) where 40% of mice tumors develop lung Metastasis. This KP model recapitulates human patients with Undifferentiated Pleomorphic Sarcoma (UPS), one of the most common subtypes of STS diagnosed in adults. RNA sequencing (RNA-Seq) was performed on paired primary and lung metastases in KP mouse sarcomas and determined that the expression of the long non-coding RNA (lncRNA) Neat1 is increased in lung metastases compared to paired primary tumors. Real time PCR (qPCR) in 22 paired KP mouse primary sarcomas and lung metastases further confirmed that Neat1 is significantly upregulated in lung metastases. In addition, RNA-Seq data from 5 pairs of human primary sarcomas and matched lung metastases also showed that NEAT1 levels are increased in lung metastases. Furthermore, NEAT1 RNA in situ hybridization (ISH) on tissue microarrays (TMAs) of human primary UPS and lung metastases determined that the expression of NEAT1 is upregulated in lung metastases. Next, CRISPR/Cas9 technology was applied to delete Neat1 in primary mouse sarcoma cells and loss of expression of Neat1 was confirmed by qPCR and northern blot in knockout (KO) clones. In addition, loss of Neat1 significantly reduced lung Metastasis in vivo following tail vein injection of these modified cells into nude mice. To further test that loss of Neat1 reduces lung Metastasis in primary sarcoma mouse model, primary tumors with Neat1 deletion are generated in GEMMs using in vivo CRISPR/Cas9 technology and KrasLSL-G12D/+; Trp53Flox/Flox; Neat1-/- (KPN) mouse model. Finally, RNA-Seq and capture hybridization analysis of RNA targets (CHART) are performed to determine mechanisms by which Neat1 regulates lung Metastasis. Overall, these results suggest that upregulation of Neat1 promotes lung Metastasis of soft tissue sarcoma and NEAT1 is a potential target to prevent or treat lung Metastasis in sarcoma patients. Citation Format: Jianguo Huang, Eric Xu, Mohit Sachdeva, Timothy Robinson, Xiaodi Qin, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene Andrulis, Jay Wunder, Tomoyo Okada, Samuel Singer, Alexander Lazar, Brian Rubin, David G. Kirsch. Long noncoding RNA NEAT1 promotes lung Metastasis of soft tissue sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 516.