Long non-coding RNAs MACC1-AS1 and FOXD2-AS1 mediate NSD2-induced cisplatin resistance in esophageal squamous cell carcinoma
The nuclear receptor-binding SET domain (NSD) protein family encoding histone lysine methyltransferases is involved in cancer progression. However, the role of NSDs in esophageal squamous cell carcinoma (ESCC) remains unclear. Here we examined the expression of NSDs in cisplatin-resistant and parent...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253120303887 |
| _version_ | 1818915244048646144 |
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| author | Wenhua Xue Zhibo Shen Lifeng Li Yuanyuan Zheng Dan Yan Quancheng Kan Jie Zhao |
| author_facet | Wenhua Xue Zhibo Shen Lifeng Li Yuanyuan Zheng Dan Yan Quancheng Kan Jie Zhao |
| author_sort | Wenhua Xue |
| collection | DOAJ |
| description | The nuclear receptor-binding SET domain (NSD) protein family encoding histone lysine methyltransferases is involved in cancer progression. However, the role of NSDs in esophageal squamous cell carcinoma (ESCC) remains unclear. Here we examined the expression of NSDs in cisplatin-resistant and parental ESCC cells and revealed the upregulation of NSD2 in cisplatin-resistant cells. Ectopic expression of NSD2 increased cisplatin resistance and attenuated cisplatin-induced apoptosis. Colony formation assay indicated that NSD2 overexpression enhanced long-term survival of ESCC cells after treatment with cisplatin. In contrast, knockdown of NSD2 inhibited ESCC cell proliferation and sensitized ESCC cells to cisplatin. Depletion of NSD2 augmented the cytotoxic effect of cisplatin on EC109 xenograft tumors. NSD2 stimulated long non-coding RNA MACC1-AS1 in ESCC cells. Knockdown of MACC1-AS1 impaired NSD2-induced cisplatin resistance. Moreover, MACC1-AS1 overexpression promoted ESCC cell proliferation and cisplatin resistance. Clinically, MACC1-AS1 was upregulated in ESCC relative to adjacent noncancerous tissues. High MACC1-AS1 levels were significantly associated with reduced overall survival of ESCC patients. There was a positive correlation between MACC1-AS1 and NSD2 expression in ESCC specimens. Taken together, MACC1-AS1 induced by NSD2 mediates resistance to cisplatin in ESCC and may represent a novel target to improve cisplatin-based chemotherapy. |
| first_indexed | 2024-12-19T23:59:11Z |
| format | Article |
| id | doaj.art-cde9cc59d6d8437f8109548f47c2778f |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-19T23:59:11Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-cde9cc59d6d8437f8109548f47c2778f2022-12-21T20:00:54ZengElsevierMolecular Therapy: Nucleic Acids2162-25312021-03-0123592602Long non-coding RNAs MACC1-AS1 and FOXD2-AS1 mediate NSD2-induced cisplatin resistance in esophageal squamous cell carcinomaWenhua Xue0Zhibo Shen1Lifeng Li2Yuanyuan Zheng3Dan Yan4Quancheng Kan5Jie Zhao6Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Internet Medical and System Applications of National Engineering Laboratory, Zhengzhou, ChinaCancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Internet Medical and System Applications of National Engineering Laboratory, Zhengzhou, ChinaCancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Internet Medical and System Applications of National Engineering Laboratory, Zhengzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China; Corresponding author: Quancheng Kan, Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Internet Medical and System Applications of National Engineering Laboratory, Zhengzhou, China; Corresponding author: Jie Zhao, Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.The nuclear receptor-binding SET domain (NSD) protein family encoding histone lysine methyltransferases is involved in cancer progression. However, the role of NSDs in esophageal squamous cell carcinoma (ESCC) remains unclear. Here we examined the expression of NSDs in cisplatin-resistant and parental ESCC cells and revealed the upregulation of NSD2 in cisplatin-resistant cells. Ectopic expression of NSD2 increased cisplatin resistance and attenuated cisplatin-induced apoptosis. Colony formation assay indicated that NSD2 overexpression enhanced long-term survival of ESCC cells after treatment with cisplatin. In contrast, knockdown of NSD2 inhibited ESCC cell proliferation and sensitized ESCC cells to cisplatin. Depletion of NSD2 augmented the cytotoxic effect of cisplatin on EC109 xenograft tumors. NSD2 stimulated long non-coding RNA MACC1-AS1 in ESCC cells. Knockdown of MACC1-AS1 impaired NSD2-induced cisplatin resistance. Moreover, MACC1-AS1 overexpression promoted ESCC cell proliferation and cisplatin resistance. Clinically, MACC1-AS1 was upregulated in ESCC relative to adjacent noncancerous tissues. High MACC1-AS1 levels were significantly associated with reduced overall survival of ESCC patients. There was a positive correlation between MACC1-AS1 and NSD2 expression in ESCC specimens. Taken together, MACC1-AS1 induced by NSD2 mediates resistance to cisplatin in ESCC and may represent a novel target to improve cisplatin-based chemotherapy.http://www.sciencedirect.com/science/article/pii/S2162253120303887apoptosiscisplatin resistanceesophageal cancerMACC1-AS1NSD2 |
| spellingShingle | Wenhua Xue Zhibo Shen Lifeng Li Yuanyuan Zheng Dan Yan Quancheng Kan Jie Zhao Long non-coding RNAs MACC1-AS1 and FOXD2-AS1 mediate NSD2-induced cisplatin resistance in esophageal squamous cell carcinoma Molecular Therapy: Nucleic Acids apoptosis cisplatin resistance esophageal cancer MACC1-AS1 NSD2 |
| title | Long non-coding RNAs MACC1-AS1 and FOXD2-AS1 mediate NSD2-induced cisplatin resistance in esophageal squamous cell carcinoma |
| title_full | Long non-coding RNAs MACC1-AS1 and FOXD2-AS1 mediate NSD2-induced cisplatin resistance in esophageal squamous cell carcinoma |
| title_fullStr | Long non-coding RNAs MACC1-AS1 and FOXD2-AS1 mediate NSD2-induced cisplatin resistance in esophageal squamous cell carcinoma |
| title_full_unstemmed | Long non-coding RNAs MACC1-AS1 and FOXD2-AS1 mediate NSD2-induced cisplatin resistance in esophageal squamous cell carcinoma |
| title_short | Long non-coding RNAs MACC1-AS1 and FOXD2-AS1 mediate NSD2-induced cisplatin resistance in esophageal squamous cell carcinoma |
| title_sort | long non coding rnas macc1 as1 and foxd2 as1 mediate nsd2 induced cisplatin resistance in esophageal squamous cell carcinoma |
| topic | apoptosis cisplatin resistance esophageal cancer MACC1-AS1 NSD2 |
| url | http://www.sciencedirect.com/science/article/pii/S2162253120303887 |
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