miR-34a-5p enhances the sensitivity of cervical cancer cells to oxaliplatin chemotherapy via targeting MDM4
Background: Cervical cancer is a common gynecologic malignancy worldwide, mainly developing in women aged about 50 years old. Currently, oxaliplatin (L-OHP) was widely used as a first-line chemotherapeutic drug to treat various tumors, including cervical cancer. The emergence of L-OHP resistance dur...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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IMR Press
2022-02-01
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| Series: | Clinical and Experimental Obstetrics & Gynecology |
| Subjects: | |
| Online Access: | https://www.imrpress.com/journal/CEOG/49/2/10.31083/j.ceog4902054 |
| _version_ | 1811256344664080384 |
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| author | Pei He XiaoLi Liu YanQin Lou ShiXiong Gong LiRong Cao |
| author_facet | Pei He XiaoLi Liu YanQin Lou ShiXiong Gong LiRong Cao |
| author_sort | Pei He |
| collection | DOAJ |
| description | Background: Cervical cancer is a common gynecologic malignancy worldwide, mainly developing in women aged about 50 years old. Currently, oxaliplatin (L-OHP) was widely used as a first-line chemotherapeutic drug to treat various tumors, including cervical cancer. The emergence of L-OHP resistance during chemotherapy has largely limited the clinical efficacy of chemotherapy. Numerous studies have demonstrated that abnormal expression of microRNAs (miRNAs) was associated with tumorigenesis and the development of cancer drug resistance. Methods: miR-34a-5p and Murine Double Minute 4 (MDM4) in cervical cancer cells was detected via RT-qPCR and Western blot assay. Cell proliferation and apoptosis were observed via ov-MDM4 and si-MDM4, Cell counting kit (CCK)-8 and flow cytometry analysis after transfection with miR-34a-5p inhibitor, miR-34a-5p mimics, respectively. Dual-luciferase reporter assay was utilized to confirm the associativity between miR-34a-5p and MDM4. Results: miR-34a-5p was significantly down-regulated whereas MDM4 was increased in cervical cancer tumor tissues and cells. Compared with Hela cells, miR-34a-5p was further decreased and MDM4 was elevated in Hela/L-OHP cells. miR-34a-5p significantly inhibited Hela/L-OHP cell viability and promoted apoptosis. Similar to the effects of miR-34a-5p, MDM4 knockdown inhibited Hela/L-OHP cell proliferation, but induced apoptosis. miR-34a-5p directly targeted MDM4 and could improve sensitivity of cervical cancer cells to L-OHP chemosensitivity by targeting MDM4 expression in vitro. Conclusions: miR-34a-5p can improve sensitivity of cervical cancer cells to L-OHP chemosensitivity, serving as a potential curative target for cervical cancer chemotherapy. |
| first_indexed | 2024-04-12T17:39:49Z |
| format | Article |
| id | doaj.art-89fee7bdf73c4f4ebf957ada46af89a4 |
| institution | Directory Open Access Journal |
| issn | 0390-6663 |
| language | English |
| last_indexed | 2024-04-12T17:39:49Z |
| publishDate | 2022-02-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Clinical and Experimental Obstetrics & Gynecology |
| spelling | doaj.art-89fee7bdf73c4f4ebf957ada46af89a42022-12-22T03:22:51ZengIMR PressClinical and Experimental Obstetrics & Gynecology0390-66632022-02-014925410.31083/j.ceog4902054S0390-6663(22)01703-1miR-34a-5p enhances the sensitivity of cervical cancer cells to oxaliplatin chemotherapy via targeting MDM4Pei He0XiaoLi Liu1YanQin Lou2ShiXiong Gong3LiRong Cao4Department of Obstetrics and Gynecology, Wuhan No.1 Hospital, 430022 Wuhan, Hubei, ChinaDepartment of Obstetrics and Gynecology, Wuhan No.1 Hospital, 430022 Wuhan, Hubei, ChinaDepartment of Obstetrics and Gynecology, Wuhan No.1 Hospital, 430022 Wuhan, Hubei, ChinaDepartment of Obstetrics and Gynecology, Wuhan No.1 Hospital, 430022 Wuhan, Hubei, ChinaDepartment of Obstetrics and Gynecology, Wuhan No.1 Hospital, 430022 Wuhan, Hubei, ChinaBackground: Cervical cancer is a common gynecologic malignancy worldwide, mainly developing in women aged about 50 years old. Currently, oxaliplatin (L-OHP) was widely used as a first-line chemotherapeutic drug to treat various tumors, including cervical cancer. The emergence of L-OHP resistance during chemotherapy has largely limited the clinical efficacy of chemotherapy. Numerous studies have demonstrated that abnormal expression of microRNAs (miRNAs) was associated with tumorigenesis and the development of cancer drug resistance. Methods: miR-34a-5p and Murine Double Minute 4 (MDM4) in cervical cancer cells was detected via RT-qPCR and Western blot assay. Cell proliferation and apoptosis were observed via ov-MDM4 and si-MDM4, Cell counting kit (CCK)-8 and flow cytometry analysis after transfection with miR-34a-5p inhibitor, miR-34a-5p mimics, respectively. Dual-luciferase reporter assay was utilized to confirm the associativity between miR-34a-5p and MDM4. Results: miR-34a-5p was significantly down-regulated whereas MDM4 was increased in cervical cancer tumor tissues and cells. Compared with Hela cells, miR-34a-5p was further decreased and MDM4 was elevated in Hela/L-OHP cells. miR-34a-5p significantly inhibited Hela/L-OHP cell viability and promoted apoptosis. Similar to the effects of miR-34a-5p, MDM4 knockdown inhibited Hela/L-OHP cell proliferation, but induced apoptosis. miR-34a-5p directly targeted MDM4 and could improve sensitivity of cervical cancer cells to L-OHP chemosensitivity by targeting MDM4 expression in vitro. Conclusions: miR-34a-5p can improve sensitivity of cervical cancer cells to L-OHP chemosensitivity, serving as a potential curative target for cervical cancer chemotherapy.https://www.imrpress.com/journal/CEOG/49/2/10.31083/j.ceog4902054cervical cancermir-34a-5pmdm4oxaliplatin |
| spellingShingle | Pei He XiaoLi Liu YanQin Lou ShiXiong Gong LiRong Cao miR-34a-5p enhances the sensitivity of cervical cancer cells to oxaliplatin chemotherapy via targeting MDM4 Clinical and Experimental Obstetrics & Gynecology cervical cancer mir-34a-5p mdm4 oxaliplatin |
| title | miR-34a-5p enhances the sensitivity of cervical cancer cells to oxaliplatin chemotherapy via targeting MDM4 |
| title_full | miR-34a-5p enhances the sensitivity of cervical cancer cells to oxaliplatin chemotherapy via targeting MDM4 |
| title_fullStr | miR-34a-5p enhances the sensitivity of cervical cancer cells to oxaliplatin chemotherapy via targeting MDM4 |
| title_full_unstemmed | miR-34a-5p enhances the sensitivity of cervical cancer cells to oxaliplatin chemotherapy via targeting MDM4 |
| title_short | miR-34a-5p enhances the sensitivity of cervical cancer cells to oxaliplatin chemotherapy via targeting MDM4 |
| title_sort | mir 34a 5p enhances the sensitivity of cervical cancer cells to oxaliplatin chemotherapy via targeting mdm4 |
| topic | cervical cancer mir-34a-5p mdm4 oxaliplatin |
| url | https://www.imrpress.com/journal/CEOG/49/2/10.31083/j.ceog4902054 |
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