The Interaction Between Long Non-coding RNA HULC and MicroRNA-622 via Transfer by Extracellular Vesicles Regulates Cell Invasion and Migration in Human Pancreatic Cancer

Although non-coding RNAs (ncRNAs) are involved in disease pathogenesis, their contributions to pancreatic ductal adenocarcinoma (PDAC) remain unclear. Recently, the interrelationship between two classes of ncRNA, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), has been reported to contribute to the epigenetic regulation of gene expression in several diseases including cancers. Moreover, some ncRNAs can be transferred by extracellular vesicles (EVs) from their donor cells to recipient cells. We previously verified that lncRNA HULC is up-regulated in PDAC cells and the intercellular transfer of HULC by EVs can promote PDAC cell invasion and migration through the induction of epithelial–mesenchymal transition (EMT). Therefore, we identified the miRNA that could target HULC and investigated the functional contributions of the miRNA–HULC interaction and EV transfer of miRNA to the EMT pathway in PDAC. Microarray analysis revealed 187 miRNAs that were decreased to <0.87-fold in Panc-1 cells treated with TGF-β compared with the control. Of these, miR-622 was predicted to target HULC directly by bioinformatics analysis. Expression of miR-622 was significantly down-regulated by TGF-β in a panel of PDAC cells. miR-622 overexpression by a miRNA mimic significantly decreased HULC expression, increased E-cadherin expression, and decreased expression of Snail, N-cadherin, and vimentin. Moreover, overexpression of miR-622 significantly reduced cell invasion and migration whereas inhibition of miR-622 increased HULC expression and promoted EMT signaling, invasion, and migration of PDAC cells. Furthermore, incubation with miR-622-overexpressing EVs could transfer miR-622, which significantly elevated miR-622 expression and decreased cell invasion and migration via inhibition of the EMT pathway in recipient PDAC cells. These results provide mechanistic insights into the development of PDAC by demonstrating that miR-622, as a miRNA downregulated by TGF-β, could target HULC and suppress invasion and migration by inhibiting EMT signaling via EV transfer. These observations may identify EV-encapsulated miRNA as a novel therapeutic target for human PDAC. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Kenji Takahashi [verfasserIn] Kazuya Koyama [verfasserIn] Yu Ota [verfasserIn] Hidetaka Iwamoto [verfasserIn] Keisuke Yamakita [verfasserIn] Satoshi Fujii [verfasserIn] Yohei Kitano [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	long non-coding RNA microRNA epithelial-mesenchymal transition invasion migration pancreatic ductal adenocarcinoma

Übergeordnetes Werk:	In: Frontiers in Oncology - Frontiers Media S.A., 2012, 10(2020)
Übergeordnetes Werk:	volume:10 ; year:2020

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fonc.2020.01013

Katalog-ID:	DOAJ036700118

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allfields	10.3389/fonc.2020.01013 doi (DE-627)DOAJ036700118 (DE-599)DOAJd484b448699b4077b4e166afedd1a030 DE-627 ger DE-627 rakwb eng RC254-282 Kenji Takahashi verfasserin aut The Interaction Between Long Non-coding RNA HULC and MicroRNA-622 via Transfer by Extracellular Vesicles Regulates Cell Invasion and Migration in Human Pancreatic Cancer 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Although non-coding RNAs (ncRNAs) are involved in disease pathogenesis, their contributions to pancreatic ductal adenocarcinoma (PDAC) remain unclear. Recently, the interrelationship between two classes of ncRNA, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), has been reported to contribute to the epigenetic regulation of gene expression in several diseases including cancers. Moreover, some ncRNAs can be transferred by extracellular vesicles (EVs) from their donor cells to recipient cells. We previously verified that lncRNA HULC is up-regulated in PDAC cells and the intercellular transfer of HULC by EVs can promote PDAC cell invasion and migration through the induction of epithelial–mesenchymal transition (EMT). Therefore, we identified the miRNA that could target HULC and investigated the functional contributions of the miRNA–HULC interaction and EV transfer of miRNA to the EMT pathway in PDAC. Microarray analysis revealed 187 miRNAs that were decreased to <0.87-fold in Panc-1 cells treated with TGF-β compared with the control. Of these, miR-622 was predicted to target HULC directly by bioinformatics analysis. Expression of miR-622 was significantly down-regulated by TGF-β in a panel of PDAC cells. miR-622 overexpression by a miRNA mimic significantly decreased HULC expression, increased E-cadherin expression, and decreased expression of Snail, N-cadherin, and vimentin. Moreover, overexpression of miR-622 significantly reduced cell invasion and migration whereas inhibition of miR-622 increased HULC expression and promoted EMT signaling, invasion, and migration of PDAC cells. Furthermore, incubation with miR-622-overexpressing EVs could transfer miR-622, which significantly elevated miR-622 expression and decreased cell invasion and migration via inhibition of the EMT pathway in recipient PDAC cells. These results provide mechanistic insights into the development of PDAC by demonstrating that miR-622, as a miRNA downregulated by TGF-β, could target HULC and suppress invasion and migration by inhibiting EMT signaling via EV transfer. These observations may identify EV-encapsulated miRNA as a novel therapeutic target for human PDAC. long non-coding RNA microRNA epithelial-mesenchymal transition invasion migration pancreatic ductal adenocarcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Kazuya Koyama verfasserin aut Yu Ota verfasserin aut Hidetaka Iwamoto verfasserin aut Keisuke Yamakita verfasserin aut Satoshi Fujii verfasserin aut Yohei Kitano verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 10(2020) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:10 year:2020 https://doi.org/10.3389/fonc.2020.01013 kostenfrei https://doaj.org/article/d484b448699b4077b4e166afedd1a030 kostenfrei https://www.frontiersin.org/article/10.3389/fonc.2020.01013/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2020
spelling	10.3389/fonc.2020.01013 doi (DE-627)DOAJ036700118 (DE-599)DOAJd484b448699b4077b4e166afedd1a030 DE-627 ger DE-627 rakwb eng RC254-282 Kenji Takahashi verfasserin aut The Interaction Between Long Non-coding RNA HULC and MicroRNA-622 via Transfer by Extracellular Vesicles Regulates Cell Invasion and Migration in Human Pancreatic Cancer 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Although non-coding RNAs (ncRNAs) are involved in disease pathogenesis, their contributions to pancreatic ductal adenocarcinoma (PDAC) remain unclear. Recently, the interrelationship between two classes of ncRNA, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), has been reported to contribute to the epigenetic regulation of gene expression in several diseases including cancers. Moreover, some ncRNAs can be transferred by extracellular vesicles (EVs) from their donor cells to recipient cells. We previously verified that lncRNA HULC is up-regulated in PDAC cells and the intercellular transfer of HULC by EVs can promote PDAC cell invasion and migration through the induction of epithelial–mesenchymal transition (EMT). Therefore, we identified the miRNA that could target HULC and investigated the functional contributions of the miRNA–HULC interaction and EV transfer of miRNA to the EMT pathway in PDAC. Microarray analysis revealed 187 miRNAs that were decreased to <0.87-fold in Panc-1 cells treated with TGF-β compared with the control. Of these, miR-622 was predicted to target HULC directly by bioinformatics analysis. Expression of miR-622 was significantly down-regulated by TGF-β in a panel of PDAC cells. miR-622 overexpression by a miRNA mimic significantly decreased HULC expression, increased E-cadherin expression, and decreased expression of Snail, N-cadherin, and vimentin. Moreover, overexpression of miR-622 significantly reduced cell invasion and migration whereas inhibition of miR-622 increased HULC expression and promoted EMT signaling, invasion, and migration of PDAC cells. Furthermore, incubation with miR-622-overexpressing EVs could transfer miR-622, which significantly elevated miR-622 expression and decreased cell invasion and migration via inhibition of the EMT pathway in recipient PDAC cells. These results provide mechanistic insights into the development of PDAC by demonstrating that miR-622, as a miRNA downregulated by TGF-β, could target HULC and suppress invasion and migration by inhibiting EMT signaling via EV transfer. These observations may identify EV-encapsulated miRNA as a novel therapeutic target for human PDAC. long non-coding RNA microRNA epithelial-mesenchymal transition invasion migration pancreatic ductal adenocarcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Kazuya Koyama verfasserin aut Yu Ota verfasserin aut Hidetaka Iwamoto verfasserin aut Keisuke Yamakita verfasserin aut Satoshi Fujii verfasserin aut Yohei Kitano verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 10(2020) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:10 year:2020 https://doi.org/10.3389/fonc.2020.01013 kostenfrei https://doaj.org/article/d484b448699b4077b4e166afedd1a030 kostenfrei https://www.frontiersin.org/article/10.3389/fonc.2020.01013/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2020
allfields_unstemmed	10.3389/fonc.2020.01013 doi (DE-627)DOAJ036700118 (DE-599)DOAJd484b448699b4077b4e166afedd1a030 DE-627 ger DE-627 rakwb eng RC254-282 Kenji Takahashi verfasserin aut The Interaction Between Long Non-coding RNA HULC and MicroRNA-622 via Transfer by Extracellular Vesicles Regulates Cell Invasion and Migration in Human Pancreatic Cancer 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Although non-coding RNAs (ncRNAs) are involved in disease pathogenesis, their contributions to pancreatic ductal adenocarcinoma (PDAC) remain unclear. Recently, the interrelationship between two classes of ncRNA, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), has been reported to contribute to the epigenetic regulation of gene expression in several diseases including cancers. Moreover, some ncRNAs can be transferred by extracellular vesicles (EVs) from their donor cells to recipient cells. We previously verified that lncRNA HULC is up-regulated in PDAC cells and the intercellular transfer of HULC by EVs can promote PDAC cell invasion and migration through the induction of epithelial–mesenchymal transition (EMT). Therefore, we identified the miRNA that could target HULC and investigated the functional contributions of the miRNA–HULC interaction and EV transfer of miRNA to the EMT pathway in PDAC. Microarray analysis revealed 187 miRNAs that were decreased to <0.87-fold in Panc-1 cells treated with TGF-β compared with the control. Of these, miR-622 was predicted to target HULC directly by bioinformatics analysis. Expression of miR-622 was significantly down-regulated by TGF-β in a panel of PDAC cells. miR-622 overexpression by a miRNA mimic significantly decreased HULC expression, increased E-cadherin expression, and decreased expression of Snail, N-cadherin, and vimentin. Moreover, overexpression of miR-622 significantly reduced cell invasion and migration whereas inhibition of miR-622 increased HULC expression and promoted EMT signaling, invasion, and migration of PDAC cells. Furthermore, incubation with miR-622-overexpressing EVs could transfer miR-622, which significantly elevated miR-622 expression and decreased cell invasion and migration via inhibition of the EMT pathway in recipient PDAC cells. These results provide mechanistic insights into the development of PDAC by demonstrating that miR-622, as a miRNA downregulated by TGF-β, could target HULC and suppress invasion and migration by inhibiting EMT signaling via EV transfer. These observations may identify EV-encapsulated miRNA as a novel therapeutic target for human PDAC. long non-coding RNA microRNA epithelial-mesenchymal transition invasion migration pancreatic ductal adenocarcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Kazuya Koyama verfasserin aut Yu Ota verfasserin aut Hidetaka Iwamoto verfasserin aut Keisuke Yamakita verfasserin aut Satoshi Fujii verfasserin aut Yohei Kitano verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 10(2020) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:10 year:2020 https://doi.org/10.3389/fonc.2020.01013 kostenfrei https://doaj.org/article/d484b448699b4077b4e166afedd1a030 kostenfrei https://www.frontiersin.org/article/10.3389/fonc.2020.01013/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2020
allfieldsGer	10.3389/fonc.2020.01013 doi (DE-627)DOAJ036700118 (DE-599)DOAJd484b448699b4077b4e166afedd1a030 DE-627 ger DE-627 rakwb eng RC254-282 Kenji Takahashi verfasserin aut The Interaction Between Long Non-coding RNA HULC and MicroRNA-622 via Transfer by Extracellular Vesicles Regulates Cell Invasion and Migration in Human Pancreatic Cancer 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Although non-coding RNAs (ncRNAs) are involved in disease pathogenesis, their contributions to pancreatic ductal adenocarcinoma (PDAC) remain unclear. Recently, the interrelationship between two classes of ncRNA, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), has been reported to contribute to the epigenetic regulation of gene expression in several diseases including cancers. Moreover, some ncRNAs can be transferred by extracellular vesicles (EVs) from their donor cells to recipient cells. We previously verified that lncRNA HULC is up-regulated in PDAC cells and the intercellular transfer of HULC by EVs can promote PDAC cell invasion and migration through the induction of epithelial–mesenchymal transition (EMT). Therefore, we identified the miRNA that could target HULC and investigated the functional contributions of the miRNA–HULC interaction and EV transfer of miRNA to the EMT pathway in PDAC. Microarray analysis revealed 187 miRNAs that were decreased to <0.87-fold in Panc-1 cells treated with TGF-β compared with the control. Of these, miR-622 was predicted to target HULC directly by bioinformatics analysis. Expression of miR-622 was significantly down-regulated by TGF-β in a panel of PDAC cells. miR-622 overexpression by a miRNA mimic significantly decreased HULC expression, increased E-cadherin expression, and decreased expression of Snail, N-cadherin, and vimentin. Moreover, overexpression of miR-622 significantly reduced cell invasion and migration whereas inhibition of miR-622 increased HULC expression and promoted EMT signaling, invasion, and migration of PDAC cells. Furthermore, incubation with miR-622-overexpressing EVs could transfer miR-622, which significantly elevated miR-622 expression and decreased cell invasion and migration via inhibition of the EMT pathway in recipient PDAC cells. These results provide mechanistic insights into the development of PDAC by demonstrating that miR-622, as a miRNA downregulated by TGF-β, could target HULC and suppress invasion and migration by inhibiting EMT signaling via EV transfer. These observations may identify EV-encapsulated miRNA as a novel therapeutic target for human PDAC. long non-coding RNA microRNA epithelial-mesenchymal transition invasion migration pancreatic ductal adenocarcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Kazuya Koyama verfasserin aut Yu Ota verfasserin aut Hidetaka Iwamoto verfasserin aut Keisuke Yamakita verfasserin aut Satoshi Fujii verfasserin aut Yohei Kitano verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 10(2020) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:10 year:2020 https://doi.org/10.3389/fonc.2020.01013 kostenfrei https://doaj.org/article/d484b448699b4077b4e166afedd1a030 kostenfrei https://www.frontiersin.org/article/10.3389/fonc.2020.01013/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2020
allfieldsSound	10.3389/fonc.2020.01013 doi (DE-627)DOAJ036700118 (DE-599)DOAJd484b448699b4077b4e166afedd1a030 DE-627 ger DE-627 rakwb eng RC254-282 Kenji Takahashi verfasserin aut The Interaction Between Long Non-coding RNA HULC and MicroRNA-622 via Transfer by Extracellular Vesicles Regulates Cell Invasion and Migration in Human Pancreatic Cancer 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Although non-coding RNAs (ncRNAs) are involved in disease pathogenesis, their contributions to pancreatic ductal adenocarcinoma (PDAC) remain unclear. Recently, the interrelationship between two classes of ncRNA, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), has been reported to contribute to the epigenetic regulation of gene expression in several diseases including cancers. Moreover, some ncRNAs can be transferred by extracellular vesicles (EVs) from their donor cells to recipient cells. We previously verified that lncRNA HULC is up-regulated in PDAC cells and the intercellular transfer of HULC by EVs can promote PDAC cell invasion and migration through the induction of epithelial–mesenchymal transition (EMT). Therefore, we identified the miRNA that could target HULC and investigated the functional contributions of the miRNA–HULC interaction and EV transfer of miRNA to the EMT pathway in PDAC. Microarray analysis revealed 187 miRNAs that were decreased to <0.87-fold in Panc-1 cells treated with TGF-β compared with the control. Of these, miR-622 was predicted to target HULC directly by bioinformatics analysis. Expression of miR-622 was significantly down-regulated by TGF-β in a panel of PDAC cells. miR-622 overexpression by a miRNA mimic significantly decreased HULC expression, increased E-cadherin expression, and decreased expression of Snail, N-cadherin, and vimentin. Moreover, overexpression of miR-622 significantly reduced cell invasion and migration whereas inhibition of miR-622 increased HULC expression and promoted EMT signaling, invasion, and migration of PDAC cells. Furthermore, incubation with miR-622-overexpressing EVs could transfer miR-622, which significantly elevated miR-622 expression and decreased cell invasion and migration via inhibition of the EMT pathway in recipient PDAC cells. These results provide mechanistic insights into the development of PDAC by demonstrating that miR-622, as a miRNA downregulated by TGF-β, could target HULC and suppress invasion and migration by inhibiting EMT signaling via EV transfer. These observations may identify EV-encapsulated miRNA as a novel therapeutic target for human PDAC. long non-coding RNA microRNA epithelial-mesenchymal transition invasion migration pancreatic ductal adenocarcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Kazuya Koyama verfasserin aut Yu Ota verfasserin aut Hidetaka Iwamoto verfasserin aut Keisuke Yamakita verfasserin aut Satoshi Fujii verfasserin aut Yohei Kitano verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 10(2020) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:10 year:2020 https://doi.org/10.3389/fonc.2020.01013 kostenfrei https://doaj.org/article/d484b448699b4077b4e166afedd1a030 kostenfrei https://www.frontiersin.org/article/10.3389/fonc.2020.01013/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2020
language	English
source	In Frontiers in Oncology 10(2020) volume:10 year:2020
sourceStr	In Frontiers in Oncology 10(2020) volume:10 year:2020
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	long non-coding RNA microRNA epithelial-mesenchymal transition invasion migration pancreatic ductal adenocarcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	Frontiers in Oncology
authorswithroles_txt_mv	Kenji Takahashi @@aut@@ Kazuya Koyama @@aut@@ Yu Ota @@aut@@ Hidetaka Iwamoto @@aut@@ Keisuke Yamakita @@aut@@ Satoshi Fujii @@aut@@ Yohei Kitano @@aut@@
publishDateDaySort_date	2020-01-01T00:00:00Z
hierarchy_top_id	684965518
id	DOAJ036700118
language_de	englisch
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topic_title	RC254-282 The Interaction Between Long Non-coding RNA HULC and MicroRNA-622 via Transfer by Extracellular Vesicles Regulates Cell Invasion and Migration in Human Pancreatic Cancer long non-coding RNA microRNA epithelial-mesenchymal transition invasion migration pancreatic ductal adenocarcinoma
topic	misc RC254-282 misc long non-coding RNA misc microRNA misc epithelial-mesenchymal transition misc invasion misc migration misc pancreatic ductal adenocarcinoma misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc long non-coding RNA misc microRNA misc epithelial-mesenchymal transition misc invasion misc migration misc pancreatic ductal adenocarcinoma misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc long non-coding RNA misc microRNA misc epithelial-mesenchymal transition misc invasion misc migration misc pancreatic ductal adenocarcinoma misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	The Interaction Between Long Non-coding RNA HULC and MicroRNA-622 via Transfer by Extracellular Vesicles Regulates Cell Invasion and Migration in Human Pancreatic Cancer
ctrlnum	(DE-627)DOAJ036700118 (DE-599)DOAJd484b448699b4077b4e166afedd1a030
title_full	The Interaction Between Long Non-coding RNA HULC and MicroRNA-622 via Transfer by Extracellular Vesicles Regulates Cell Invasion and Migration in Human Pancreatic Cancer
author_sort	Kenji Takahashi
journal	Frontiers in Oncology
journalStr	Frontiers in Oncology
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contenttype_str_mv	txt
author_browse	Kenji Takahashi Kazuya Koyama Yu Ota Hidetaka Iwamoto Keisuke Yamakita Satoshi Fujii Yohei Kitano
container_volume	10
class	RC254-282
format_se	Elektronische Aufsätze
author-letter	Kenji Takahashi
doi_str_mv	10.3389/fonc.2020.01013
author2-role	verfasserin
title_sort	interaction between long non-coding rna hulc and microrna-622 via transfer by extracellular vesicles regulates cell invasion and migration in human pancreatic cancer
callnumber	RC254-282
title_auth	The Interaction Between Long Non-coding RNA HULC and MicroRNA-622 via Transfer by Extracellular Vesicles Regulates Cell Invasion and Migration in Human Pancreatic Cancer
abstract	Although non-coding RNAs (ncRNAs) are involved in disease pathogenesis, their contributions to pancreatic ductal adenocarcinoma (PDAC) remain unclear. Recently, the interrelationship between two classes of ncRNA, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), has been reported to contribute to the epigenetic regulation of gene expression in several diseases including cancers. Moreover, some ncRNAs can be transferred by extracellular vesicles (EVs) from their donor cells to recipient cells. We previously verified that lncRNA HULC is up-regulated in PDAC cells and the intercellular transfer of HULC by EVs can promote PDAC cell invasion and migration through the induction of epithelial–mesenchymal transition (EMT). Therefore, we identified the miRNA that could target HULC and investigated the functional contributions of the miRNA–HULC interaction and EV transfer of miRNA to the EMT pathway in PDAC. Microarray analysis revealed 187 miRNAs that were decreased to <0.87-fold in Panc-1 cells treated with TGF-β compared with the control. Of these, miR-622 was predicted to target HULC directly by bioinformatics analysis. Expression of miR-622 was significantly down-regulated by TGF-β in a panel of PDAC cells. miR-622 overexpression by a miRNA mimic significantly decreased HULC expression, increased E-cadherin expression, and decreased expression of Snail, N-cadherin, and vimentin. Moreover, overexpression of miR-622 significantly reduced cell invasion and migration whereas inhibition of miR-622 increased HULC expression and promoted EMT signaling, invasion, and migration of PDAC cells. Furthermore, incubation with miR-622-overexpressing EVs could transfer miR-622, which significantly elevated miR-622 expression and decreased cell invasion and migration via inhibition of the EMT pathway in recipient PDAC cells. These results provide mechanistic insights into the development of PDAC by demonstrating that miR-622, as a miRNA downregulated by TGF-β, could target HULC and suppress invasion and migration by inhibiting EMT signaling via EV transfer. These observations may identify EV-encapsulated miRNA as a novel therapeutic target for human PDAC.
abstractGer	Although non-coding RNAs (ncRNAs) are involved in disease pathogenesis, their contributions to pancreatic ductal adenocarcinoma (PDAC) remain unclear. Recently, the interrelationship between two classes of ncRNA, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), has been reported to contribute to the epigenetic regulation of gene expression in several diseases including cancers. Moreover, some ncRNAs can be transferred by extracellular vesicles (EVs) from their donor cells to recipient cells. We previously verified that lncRNA HULC is up-regulated in PDAC cells and the intercellular transfer of HULC by EVs can promote PDAC cell invasion and migration through the induction of epithelial–mesenchymal transition (EMT). Therefore, we identified the miRNA that could target HULC and investigated the functional contributions of the miRNA–HULC interaction and EV transfer of miRNA to the EMT pathway in PDAC. Microarray analysis revealed 187 miRNAs that were decreased to <0.87-fold in Panc-1 cells treated with TGF-β compared with the control. Of these, miR-622 was predicted to target HULC directly by bioinformatics analysis. Expression of miR-622 was significantly down-regulated by TGF-β in a panel of PDAC cells. miR-622 overexpression by a miRNA mimic significantly decreased HULC expression, increased E-cadherin expression, and decreased expression of Snail, N-cadherin, and vimentin. Moreover, overexpression of miR-622 significantly reduced cell invasion and migration whereas inhibition of miR-622 increased HULC expression and promoted EMT signaling, invasion, and migration of PDAC cells. Furthermore, incubation with miR-622-overexpressing EVs could transfer miR-622, which significantly elevated miR-622 expression and decreased cell invasion and migration via inhibition of the EMT pathway in recipient PDAC cells. These results provide mechanistic insights into the development of PDAC by demonstrating that miR-622, as a miRNA downregulated by TGF-β, could target HULC and suppress invasion and migration by inhibiting EMT signaling via EV transfer. These observations may identify EV-encapsulated miRNA as a novel therapeutic target for human PDAC.
abstract_unstemmed	Although non-coding RNAs (ncRNAs) are involved in disease pathogenesis, their contributions to pancreatic ductal adenocarcinoma (PDAC) remain unclear. Recently, the interrelationship between two classes of ncRNA, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), has been reported to contribute to the epigenetic regulation of gene expression in several diseases including cancers. Moreover, some ncRNAs can be transferred by extracellular vesicles (EVs) from their donor cells to recipient cells. We previously verified that lncRNA HULC is up-regulated in PDAC cells and the intercellular transfer of HULC by EVs can promote PDAC cell invasion and migration through the induction of epithelial–mesenchymal transition (EMT). Therefore, we identified the miRNA that could target HULC and investigated the functional contributions of the miRNA–HULC interaction and EV transfer of miRNA to the EMT pathway in PDAC. Microarray analysis revealed 187 miRNAs that were decreased to <0.87-fold in Panc-1 cells treated with TGF-β compared with the control. Of these, miR-622 was predicted to target HULC directly by bioinformatics analysis. Expression of miR-622 was significantly down-regulated by TGF-β in a panel of PDAC cells. miR-622 overexpression by a miRNA mimic significantly decreased HULC expression, increased E-cadherin expression, and decreased expression of Snail, N-cadherin, and vimentin. Moreover, overexpression of miR-622 significantly reduced cell invasion and migration whereas inhibition of miR-622 increased HULC expression and promoted EMT signaling, invasion, and migration of PDAC cells. Furthermore, incubation with miR-622-overexpressing EVs could transfer miR-622, which significantly elevated miR-622 expression and decreased cell invasion and migration via inhibition of the EMT pathway in recipient PDAC cells. These results provide mechanistic insights into the development of PDAC by demonstrating that miR-622, as a miRNA downregulated by TGF-β, could target HULC and suppress invasion and migration by inhibiting EMT signaling via EV transfer. These observations may identify EV-encapsulated miRNA as a novel therapeutic target for human PDAC.
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700
title_short	The Interaction Between Long Non-coding RNA HULC and MicroRNA-622 via Transfer by Extracellular Vesicles Regulates Cell Invasion and Migration in Human Pancreatic Cancer
url	https://doi.org/10.3389/fonc.2020.01013 https://doaj.org/article/d484b448699b4077b4e166afedd1a030 https://www.frontiersin.org/article/10.3389/fonc.2020.01013/full https://doaj.org/toc/2234-943X
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author2	Kazuya Koyama Yu Ota Hidetaka Iwamoto Keisuke Yamakita Satoshi Fujii Yohei Kitano
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doi_str	10.3389/fonc.2020.01013
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up_date	2024-07-03T22:01:54.206Z
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