A MicroRNA Cluster in the DLK1-DIO3 Imprinted Region on Chromosome 14q32.2 Is Dysregulated in Metastatic Hepatoblastomas
Hepatoblastoma (HB) is the most common malignant liver neoplasm in children. Despite progress in HB therapy, outcomes for patients with metastatic disease remain poor. Dysregulation of miRNA expression is one of the potential epigenetic mechanisms associated with pathogenesis of HB. However, miRNA p...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-11-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.513601/full |
| _version_ | 1818192521257287680 |
|---|---|
| author | Shohei Honda Aniruddha Chatterjee Anna L. Leichter Hisayuki Miyagi Masashi Minato Sunao Fujiyoshi Momoko Ara Norihiko Kitagawa Mio Tanaka Yukichi Tanaka Masato Shinkai Kanako C. Hatanaka Akinobu Taketomi Michael R. Eccles |
| author_facet | Shohei Honda Aniruddha Chatterjee Anna L. Leichter Hisayuki Miyagi Masashi Minato Sunao Fujiyoshi Momoko Ara Norihiko Kitagawa Mio Tanaka Yukichi Tanaka Masato Shinkai Kanako C. Hatanaka Akinobu Taketomi Michael R. Eccles |
| author_sort | Shohei Honda |
| collection | DOAJ |
| description | Hepatoblastoma (HB) is the most common malignant liver neoplasm in children. Despite progress in HB therapy, outcomes for patients with metastatic disease remain poor. Dysregulation of miRNA expression is one of the potential epigenetic mechanisms associated with pathogenesis of HB. However, miRNA profiles related to the different stages of HB tissues and cells, in particular of lung metastatic tumor cells, are unknown. In the present study, using array-based miRNA expression and DNA methylation analysis on formalin-fixed paraffin-embedded tissues, we aimed to identify miRNA changes that can discriminate between lung metastatic tumors, primary tumors (fetal and embryonal subtypes), and nontumorous surrounding livers. Our analysis demonstrated that a large cluster of microRNAs and snoRNAs located within the 14q32.2 DLK1-DIO3 region showed a strikingly upregulated expression pattern in HB tumors, especially metastatic tumors, compared to normal liver tissues. This revealed dysregulation of miRNAs similar to that seen in a malignant stem-like subtype of hepatocellular carcinoma associated with poor prognosis. These findings in HB mirror similar findings made in multiple other cancer types. With further analysis this may in future allow stratification of different stages and types of HB tumors based on their miRNA profiles, which could lead to new approaches to diagnosis and treatment in progressive HB patients. |
| first_indexed | 2024-12-12T00:31:49Z |
| format | Article |
| id | doaj.art-10b3d1efe74e41d580e9a8cb4f6c74b7 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T00:31:49Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-10b3d1efe74e41d580e9a8cb4f6c74b72022-12-22T00:44:28ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-11-011010.3389/fonc.2020.513601513601A MicroRNA Cluster in the DLK1-DIO3 Imprinted Region on Chromosome 14q32.2 Is Dysregulated in Metastatic HepatoblastomasShohei Honda0Aniruddha Chatterjee1Anna L. Leichter2Hisayuki Miyagi3Masashi Minato4Sunao Fujiyoshi5Momoko Ara6Norihiko Kitagawa7Mio Tanaka8Yukichi Tanaka9Masato Shinkai10Kanako C. Hatanaka11Akinobu Taketomi12Michael R. Eccles13Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, JapanDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New ZealandDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New ZealandDepartment of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, JapanDepartment of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, JapanDepartment of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, JapanDepartment of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, JapanDepartment of Surgery, Kanagawa Children’s Medical Center, Yokohama, JapanDepartment of Pathology, Kanagawa Children’s Medical Center, Yokohama, JapanDepartment of Pathology, Kanagawa Children’s Medical Center, Yokohama, JapanDepartment of Surgery, Kanagawa Children’s Medical Center, Yokohama, JapanDepartment of Surgical Pathology, Hokkaido University Hospital, Sapporo, JapanDepartment of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, JapanDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New ZealandHepatoblastoma (HB) is the most common malignant liver neoplasm in children. Despite progress in HB therapy, outcomes for patients with metastatic disease remain poor. Dysregulation of miRNA expression is one of the potential epigenetic mechanisms associated with pathogenesis of HB. However, miRNA profiles related to the different stages of HB tissues and cells, in particular of lung metastatic tumor cells, are unknown. In the present study, using array-based miRNA expression and DNA methylation analysis on formalin-fixed paraffin-embedded tissues, we aimed to identify miRNA changes that can discriminate between lung metastatic tumors, primary tumors (fetal and embryonal subtypes), and nontumorous surrounding livers. Our analysis demonstrated that a large cluster of microRNAs and snoRNAs located within the 14q32.2 DLK1-DIO3 region showed a strikingly upregulated expression pattern in HB tumors, especially metastatic tumors, compared to normal liver tissues. This revealed dysregulation of miRNAs similar to that seen in a malignant stem-like subtype of hepatocellular carcinoma associated with poor prognosis. These findings in HB mirror similar findings made in multiple other cancer types. With further analysis this may in future allow stratification of different stages and types of HB tumors based on their miRNA profiles, which could lead to new approaches to diagnosis and treatment in progressive HB patients.https://www.frontiersin.org/articles/10.3389/fonc.2020.513601/fullepigeneticssmall nucleolar RNAsmicroRNAshepatoblastoma14q32-encoded imprinted cluster genes |
| spellingShingle | Shohei Honda Aniruddha Chatterjee Anna L. Leichter Hisayuki Miyagi Masashi Minato Sunao Fujiyoshi Momoko Ara Norihiko Kitagawa Mio Tanaka Yukichi Tanaka Masato Shinkai Kanako C. Hatanaka Akinobu Taketomi Michael R. Eccles A MicroRNA Cluster in the DLK1-DIO3 Imprinted Region on Chromosome 14q32.2 Is Dysregulated in Metastatic Hepatoblastomas Frontiers in Oncology epigenetics small nucleolar RNAs microRNAs hepatoblastoma 14q32-encoded imprinted cluster genes |
| title | A MicroRNA Cluster in the DLK1-DIO3 Imprinted Region on Chromosome 14q32.2 Is Dysregulated in Metastatic Hepatoblastomas |
| title_full | A MicroRNA Cluster in the DLK1-DIO3 Imprinted Region on Chromosome 14q32.2 Is Dysregulated in Metastatic Hepatoblastomas |
| title_fullStr | A MicroRNA Cluster in the DLK1-DIO3 Imprinted Region on Chromosome 14q32.2 Is Dysregulated in Metastatic Hepatoblastomas |
| title_full_unstemmed | A MicroRNA Cluster in the DLK1-DIO3 Imprinted Region on Chromosome 14q32.2 Is Dysregulated in Metastatic Hepatoblastomas |
| title_short | A MicroRNA Cluster in the DLK1-DIO3 Imprinted Region on Chromosome 14q32.2 Is Dysregulated in Metastatic Hepatoblastomas |
| title_sort | microrna cluster in the dlk1 dio3 imprinted region on chromosome 14q32 2 is dysregulated in metastatic hepatoblastomas |
| topic | epigenetics small nucleolar RNAs microRNAs hepatoblastoma 14q32-encoded imprinted cluster genes |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.513601/full |
| work_keys_str_mv | AT shoheihonda amicrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT aniruddhachatterjee amicrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT annalleichter amicrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT hisayukimiyagi amicrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT masashiminato amicrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT sunaofujiyoshi amicrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT momokoara amicrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT norihikokitagawa amicrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT miotanaka amicrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT yukichitanaka amicrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT masatoshinkai amicrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT kanakochatanaka amicrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT akinobutaketomi amicrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT michaelreccles amicrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT shoheihonda micrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT aniruddhachatterjee micrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT annalleichter micrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT hisayukimiyagi micrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT masashiminato micrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT sunaofujiyoshi micrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT momokoara micrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT norihikokitagawa micrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT miotanaka micrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT yukichitanaka micrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT masatoshinkai micrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT kanakochatanaka micrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT akinobutaketomi micrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas AT michaelreccles micrornaclusterinthedlk1dio3imprintedregiononchromosome14q322isdysregulatedinmetastatichepatoblastomas |