METTL3 increases cisplatin chemosensitivity of cervical cancer cells via downregulation of the activity of RAGE
Cervical cancer is the most common gynecologic malignancy worldwide. Methyltransferase-like 3 (METTL3) is involved in tumorigenesis; however, it is unclear whether METTL3 plays a potential role in regulating cisplatin (DDP) resistance. Therefore, the role of METTL3 in the regulation of cisplatin sen...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-09-01
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| Series: | Molecular Therapy: Oncolytics |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770521000796 |
| _version_ | 1819140035701637120 |
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| author | Ruyi Li Yizuo Song Xin Chen Man Chu Zhi-wei Wang Xueqiong Zhu |
| author_facet | Ruyi Li Yizuo Song Xin Chen Man Chu Zhi-wei Wang Xueqiong Zhu |
| author_sort | Ruyi Li |
| collection | DOAJ |
| description | Cervical cancer is the most common gynecologic malignancy worldwide. Methyltransferase-like 3 (METTL3) is involved in tumorigenesis; however, it is unclear whether METTL3 plays a potential role in regulating cisplatin (DDP) resistance. Therefore, the role of METTL3 in the regulation of cisplatin sensitivity in cervical cancer cells was determined. Our immunohistochemistry (IHC) data showed that METTL3 was highly expressed in para-cancerous compared with cervical cancer tissues. Furthermore, METTL3 overexpression inhibited viability and increased cisplatin sensitivity of cervical cancer cells in vitro. Overexpression of METTL3 inhibited tumor growth in vivo. IHC results showed that the receptor for advanced glycation and products (RAGE) had higher expression levels in cervical cancer tissues. RAGE downregulation increased cell sensitivity to cisplatin treatment. Moreover, the combination of FPS-ZM1 with cisplatin was more effective in inhibiting cell viability as compared with FPS-ZM1 or cisplatin only. Additionally, METTL3 reduced RAGE expression in cervical cancer cells. Overexpression of METTL3 downregulated RAGE expression and caused more sensitivity to cisplatin treatment in the SiHa-DDP cell line. METTL3 inhibited cell viability and increased apoptosis as well as enhanced the sensitivity of cisplatin via downregulating RAGE expression in cervical cancer cells. |
| first_indexed | 2024-12-22T11:32:09Z |
| format | Article |
| id | doaj.art-2814340d556f4942869ffc090d7f0238 |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-12-22T11:32:09Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-2814340d556f4942869ffc090d7f02382022-12-21T18:27:35ZengElsevierMolecular Therapy: Oncolytics2372-77052021-09-0122245255METTL3 increases cisplatin chemosensitivity of cervical cancer cells via downregulation of the activity of RAGERuyi Li0Yizuo Song1Xin Chen2Man Chu3Zhi-wei Wang4Xueqiong Zhu5Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, ChinaCenter for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, ChinaCenter for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, ChinaCenter for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, ChinaCenter for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China; Corresponding author: Zhi-wei Wang, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou 325027, Zhejiang, China.Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China; Corresponding author: Xueqiong Zhu, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou 325027, Zhejiang, China.Cervical cancer is the most common gynecologic malignancy worldwide. Methyltransferase-like 3 (METTL3) is involved in tumorigenesis; however, it is unclear whether METTL3 plays a potential role in regulating cisplatin (DDP) resistance. Therefore, the role of METTL3 in the regulation of cisplatin sensitivity in cervical cancer cells was determined. Our immunohistochemistry (IHC) data showed that METTL3 was highly expressed in para-cancerous compared with cervical cancer tissues. Furthermore, METTL3 overexpression inhibited viability and increased cisplatin sensitivity of cervical cancer cells in vitro. Overexpression of METTL3 inhibited tumor growth in vivo. IHC results showed that the receptor for advanced glycation and products (RAGE) had higher expression levels in cervical cancer tissues. RAGE downregulation increased cell sensitivity to cisplatin treatment. Moreover, the combination of FPS-ZM1 with cisplatin was more effective in inhibiting cell viability as compared with FPS-ZM1 or cisplatin only. Additionally, METTL3 reduced RAGE expression in cervical cancer cells. Overexpression of METTL3 downregulated RAGE expression and caused more sensitivity to cisplatin treatment in the SiHa-DDP cell line. METTL3 inhibited cell viability and increased apoptosis as well as enhanced the sensitivity of cisplatin via downregulating RAGE expression in cervical cancer cells.http://www.sciencedirect.com/science/article/pii/S2372770521000796METTL3RAGEcisplatinchemosensitivitycervical cancerproliferation |
| spellingShingle | Ruyi Li Yizuo Song Xin Chen Man Chu Zhi-wei Wang Xueqiong Zhu METTL3 increases cisplatin chemosensitivity of cervical cancer cells via downregulation of the activity of RAGE Molecular Therapy: Oncolytics METTL3 RAGE cisplatin chemosensitivity cervical cancer proliferation |
| title | METTL3 increases cisplatin chemosensitivity of cervical cancer cells via downregulation of the activity of RAGE |
| title_full | METTL3 increases cisplatin chemosensitivity of cervical cancer cells via downregulation of the activity of RAGE |
| title_fullStr | METTL3 increases cisplatin chemosensitivity of cervical cancer cells via downregulation of the activity of RAGE |
| title_full_unstemmed | METTL3 increases cisplatin chemosensitivity of cervical cancer cells via downregulation of the activity of RAGE |
| title_short | METTL3 increases cisplatin chemosensitivity of cervical cancer cells via downregulation of the activity of RAGE |
| title_sort | mettl3 increases cisplatin chemosensitivity of cervical cancer cells via downregulation of the activity of rage |
| topic | METTL3 RAGE cisplatin chemosensitivity cervical cancer proliferation |
| url | http://www.sciencedirect.com/science/article/pii/S2372770521000796 |
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