A novel upregulated hsa_circ_0032746 regulates the oncogenesis of esophageal squamous cell carcinoma by regulating miR-4270/MCM3 axis
Abstract Introduction Circular RNAs (CircRNA) have emerged as an interest of research in recent years due to its regulatory role in various kinds of cancers of human body. Esophageal squamous cell carcinoma (ESCC) is one of the major disease subtype in Asian countries, including China. CircRNAs are...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-01-01
|
| Series: | Human Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40246-023-00564-7 |
| _version_ | 1797355623574142976 |
|---|---|
| author | Sachin Mulmi Shrestha Xin Fang Hui Ye Lihua Ren Qinghua Ji Ruihua Shi |
| author_facet | Sachin Mulmi Shrestha Xin Fang Hui Ye Lihua Ren Qinghua Ji Ruihua Shi |
| author_sort | Sachin Mulmi Shrestha |
| collection | DOAJ |
| description | Abstract Introduction Circular RNAs (CircRNA) have emerged as an interest of research in recent years due to its regulatory role in various kinds of cancers of human body. Esophageal squamous cell carcinoma (ESCC) is one of the major disease subtype in Asian countries, including China. CircRNAs are formed by back-splicing covalently joined 3′- and 5′- ends rather than canonical splicing and are found to have binding affinity with miRNAs that conjointly contribute to oncogenesis. Materials and methods 4 pairs of normal, cancer adjacent tissues and cancer tissues were analyzed by high-throughput RNA sequencing and 84 differentially upregulated circRNAs were detected in cancer tissues. hsa_circ_0032746 was silenced by siRNA and lentivirus and then further proliferation, migration and invasion were performed by CCK-8 and transwell assays. Bioinformatic analysis predicted binding affinity of circRNA/miRNA/mRNA axis. Results After qPCR validation, we selected a novel upregulated hsa_circ_0032746 to explore its biogenetic functions which showed high expression in cancer tissues but not in cancer adjacent tissues. The clinicopathological relation of hsa_circ_0032746 showed positive correlation with the tumor location (P = 0.026) and gender (P = 0.05). We also predicted that hsa_circ_0032746 could sponge with microRNA. Bioinformatic analysis predicted 11 microRNA response element (MRE) sequences of hsa_circ_0032746 and dual luciferase reporter assay confirmed binding affinity with miR4270 evidencing further study of circRNA/miRNA role. The knockdown of hsa_circ_0032746 by siRNA and lentivirus demonstrated that proliferation, invasion and migration of ESCC were inhibited in vitro and vivo experiments. Bioinformatic analysis further predicted MCM3 as a target of miR-4270 and was found upregulated in ESCC upon validation. miR4270 mimic decreased the level of hsa_circ_0032746 and MCM3 while further rescue experiments demonstrated that hsa_circ_0032746 was dependent on miR4270/MCM3 axis on the development process of ESCC. Conclusion We revealed for the first time that circ_0032746/mir4270/MCM3 contributes in proliferation, migration and invasion of ESCC and could have potential prognostic and therapeutic significance. |
| first_indexed | 2024-03-08T14:13:49Z |
| format | Article |
| id | doaj.art-1604481d86d14722beae37b96ce886fd |
| institution | Directory Open Access Journal |
| issn | 1479-7364 |
| language | English |
| last_indexed | 2024-03-08T14:13:49Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Human Genomics |
| spelling | doaj.art-1604481d86d14722beae37b96ce886fd2024-01-14T12:29:52ZengBMCHuman Genomics1479-73642024-01-0118111410.1186/s40246-023-00564-7A novel upregulated hsa_circ_0032746 regulates the oncogenesis of esophageal squamous cell carcinoma by regulating miR-4270/MCM3 axisSachin Mulmi Shrestha0Xin Fang1Hui Ye2Lihua Ren3Qinghua Ji4Ruihua Shi5Department of Gastroenterology, School of Medicine, Southeast UniversityDepartment of Gastroenterology, School of Medicine, Southeast UniversityDepartment of Gastroenterology, Zhongda Hospital Affiliated to Southeast UniversityDepartment of Gastroenterology, Zhongda Hospital Affiliated to Southeast UniversityDepartment of Gastroenterology, Zhongda Hospital Affiliated to Southeast UniversityDepartment of Gastroenterology, School of Medicine, Southeast UniversityAbstract Introduction Circular RNAs (CircRNA) have emerged as an interest of research in recent years due to its regulatory role in various kinds of cancers of human body. Esophageal squamous cell carcinoma (ESCC) is one of the major disease subtype in Asian countries, including China. CircRNAs are formed by back-splicing covalently joined 3′- and 5′- ends rather than canonical splicing and are found to have binding affinity with miRNAs that conjointly contribute to oncogenesis. Materials and methods 4 pairs of normal, cancer adjacent tissues and cancer tissues were analyzed by high-throughput RNA sequencing and 84 differentially upregulated circRNAs were detected in cancer tissues. hsa_circ_0032746 was silenced by siRNA and lentivirus and then further proliferation, migration and invasion were performed by CCK-8 and transwell assays. Bioinformatic analysis predicted binding affinity of circRNA/miRNA/mRNA axis. Results After qPCR validation, we selected a novel upregulated hsa_circ_0032746 to explore its biogenetic functions which showed high expression in cancer tissues but not in cancer adjacent tissues. The clinicopathological relation of hsa_circ_0032746 showed positive correlation with the tumor location (P = 0.026) and gender (P = 0.05). We also predicted that hsa_circ_0032746 could sponge with microRNA. Bioinformatic analysis predicted 11 microRNA response element (MRE) sequences of hsa_circ_0032746 and dual luciferase reporter assay confirmed binding affinity with miR4270 evidencing further study of circRNA/miRNA role. The knockdown of hsa_circ_0032746 by siRNA and lentivirus demonstrated that proliferation, invasion and migration of ESCC were inhibited in vitro and vivo experiments. Bioinformatic analysis further predicted MCM3 as a target of miR-4270 and was found upregulated in ESCC upon validation. miR4270 mimic decreased the level of hsa_circ_0032746 and MCM3 while further rescue experiments demonstrated that hsa_circ_0032746 was dependent on miR4270/MCM3 axis on the development process of ESCC. Conclusion We revealed for the first time that circ_0032746/mir4270/MCM3 contributes in proliferation, migration and invasion of ESCC and could have potential prognostic and therapeutic significance.https://doi.org/10.1186/s40246-023-00564-7circRNAEsophageal squamous cell carcinomamicroRNAUpregulated |
| spellingShingle | Sachin Mulmi Shrestha Xin Fang Hui Ye Lihua Ren Qinghua Ji Ruihua Shi A novel upregulated hsa_circ_0032746 regulates the oncogenesis of esophageal squamous cell carcinoma by regulating miR-4270/MCM3 axis Human Genomics circRNA Esophageal squamous cell carcinoma microRNA Upregulated |
| title | A novel upregulated hsa_circ_0032746 regulates the oncogenesis of esophageal squamous cell carcinoma by regulating miR-4270/MCM3 axis |
| title_full | A novel upregulated hsa_circ_0032746 regulates the oncogenesis of esophageal squamous cell carcinoma by regulating miR-4270/MCM3 axis |
| title_fullStr | A novel upregulated hsa_circ_0032746 regulates the oncogenesis of esophageal squamous cell carcinoma by regulating miR-4270/MCM3 axis |
| title_full_unstemmed | A novel upregulated hsa_circ_0032746 regulates the oncogenesis of esophageal squamous cell carcinoma by regulating miR-4270/MCM3 axis |
| title_short | A novel upregulated hsa_circ_0032746 regulates the oncogenesis of esophageal squamous cell carcinoma by regulating miR-4270/MCM3 axis |
| title_sort | novel upregulated hsa circ 0032746 regulates the oncogenesis of esophageal squamous cell carcinoma by regulating mir 4270 mcm3 axis |
| topic | circRNA Esophageal squamous cell carcinoma microRNA Upregulated |
| url | https://doi.org/10.1186/s40246-023-00564-7 |
| work_keys_str_mv | AT sachinmulmishrestha anovelupregulatedhsacirc0032746regulatestheoncogenesisofesophagealsquamouscellcarcinomabyregulatingmir4270mcm3axis AT xinfang anovelupregulatedhsacirc0032746regulatestheoncogenesisofesophagealsquamouscellcarcinomabyregulatingmir4270mcm3axis AT huiye anovelupregulatedhsacirc0032746regulatestheoncogenesisofesophagealsquamouscellcarcinomabyregulatingmir4270mcm3axis AT lihuaren anovelupregulatedhsacirc0032746regulatestheoncogenesisofesophagealsquamouscellcarcinomabyregulatingmir4270mcm3axis AT qinghuaji anovelupregulatedhsacirc0032746regulatestheoncogenesisofesophagealsquamouscellcarcinomabyregulatingmir4270mcm3axis AT ruihuashi anovelupregulatedhsacirc0032746regulatestheoncogenesisofesophagealsquamouscellcarcinomabyregulatingmir4270mcm3axis AT sachinmulmishrestha novelupregulatedhsacirc0032746regulatestheoncogenesisofesophagealsquamouscellcarcinomabyregulatingmir4270mcm3axis AT xinfang novelupregulatedhsacirc0032746regulatestheoncogenesisofesophagealsquamouscellcarcinomabyregulatingmir4270mcm3axis AT huiye novelupregulatedhsacirc0032746regulatestheoncogenesisofesophagealsquamouscellcarcinomabyregulatingmir4270mcm3axis AT lihuaren novelupregulatedhsacirc0032746regulatestheoncogenesisofesophagealsquamouscellcarcinomabyregulatingmir4270mcm3axis AT qinghuaji novelupregulatedhsacirc0032746regulatestheoncogenesisofesophagealsquamouscellcarcinomabyregulatingmir4270mcm3axis AT ruihuashi novelupregulatedhsacirc0032746regulatestheoncogenesisofesophagealsquamouscellcarcinomabyregulatingmir4270mcm3axis |