PDHB-AS suppresses cervical cancer progression and cisplatin resistance via inhibition on Wnt/β-catenin pathway
Abstract Cervical cancer (CC) is the most prevalent gynecological malignancy occurring in the cervix. Long non-coding RNAs (lncRNAs) can act as oncogenes or anti-oncogenes in CC development. Here, we investigated the functional role and detailed mechanism of lncRNA pyruvate dehydrogenase E1 subunit...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-02-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05547-5 |
| _version_ | 1811165737505521664 |
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| author | Chi Chi Wenjie Hou Yi Zhang Jie Chen Zongji Shen Youguo Chen Min Li |
| author_facet | Chi Chi Wenjie Hou Yi Zhang Jie Chen Zongji Shen Youguo Chen Min Li |
| author_sort | Chi Chi |
| collection | DOAJ |
| description | Abstract Cervical cancer (CC) is the most prevalent gynecological malignancy occurring in the cervix. Long non-coding RNAs (lncRNAs) can act as oncogenes or anti-oncogenes in CC development. Here, we investigated the functional role and detailed mechanism of lncRNA pyruvate dehydrogenase E1 subunit beta antisense (PDHB-AS) in CC. At first, we found that PDHB-AS was significantly down-regulated in CC cells. Besides, overexpression of PDHB-AS repressed CC cell malignant behaviors. HKF-derived exosomes carried miR-4536-5p to CC cells and thereby inhibited PDHB-AS expression. Moreover, PDHB-AS inactivated the Wnt/β-catenin pathway via impeding the nuclear translocation of β-catenin in CC cells. In addition, miR-582-5p could bind with both PDHB-AS and Dickkopf-1 (DKK1). PDHB-AS recruited poly(A) binding protein cytoplasmic 1 (PABPC1) to inhibit Wnt7b expression. PDHB-AS interacted with RNA-binding motif protein X-linked (RBMX) to regulate cisplatin resistance in CC. Finally, we conducted in vivo experiments to confirm that HKF promoted CC tumor growth whereas PDHB-AS suppressed CC tumor growth. Collectively, PDHB-AS plays a tumor-suppressive role in the progression of CC, which suggests the therapeutic potential of PDHB-AS for CC. |
| first_indexed | 2024-04-10T15:41:28Z |
| format | Article |
| id | doaj.art-e6577c17a36941349225fd3aca64f5d7 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-10T15:41:28Z |
| publishDate | 2023-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-e6577c17a36941349225fd3aca64f5d72023-02-12T12:24:09ZengNature Publishing GroupCell Death and Disease2041-48892023-02-0114211110.1038/s41419-022-05547-5PDHB-AS suppresses cervical cancer progression and cisplatin resistance via inhibition on Wnt/β-catenin pathwayChi Chi0Wenjie Hou1Yi Zhang2Jie Chen3Zongji Shen4Youguo Chen5Min Li6Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow UniversityDepartment of Obstetrics and Gynecology, Dushu Lake Hospital Affiliated to Soochow UniversityDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow UniversityDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow UniversityDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow UniversityDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow UniversityDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow UniversityAbstract Cervical cancer (CC) is the most prevalent gynecological malignancy occurring in the cervix. Long non-coding RNAs (lncRNAs) can act as oncogenes or anti-oncogenes in CC development. Here, we investigated the functional role and detailed mechanism of lncRNA pyruvate dehydrogenase E1 subunit beta antisense (PDHB-AS) in CC. At first, we found that PDHB-AS was significantly down-regulated in CC cells. Besides, overexpression of PDHB-AS repressed CC cell malignant behaviors. HKF-derived exosomes carried miR-4536-5p to CC cells and thereby inhibited PDHB-AS expression. Moreover, PDHB-AS inactivated the Wnt/β-catenin pathway via impeding the nuclear translocation of β-catenin in CC cells. In addition, miR-582-5p could bind with both PDHB-AS and Dickkopf-1 (DKK1). PDHB-AS recruited poly(A) binding protein cytoplasmic 1 (PABPC1) to inhibit Wnt7b expression. PDHB-AS interacted with RNA-binding motif protein X-linked (RBMX) to regulate cisplatin resistance in CC. Finally, we conducted in vivo experiments to confirm that HKF promoted CC tumor growth whereas PDHB-AS suppressed CC tumor growth. Collectively, PDHB-AS plays a tumor-suppressive role in the progression of CC, which suggests the therapeutic potential of PDHB-AS for CC.https://doi.org/10.1038/s41419-022-05547-5 |
| spellingShingle | Chi Chi Wenjie Hou Yi Zhang Jie Chen Zongji Shen Youguo Chen Min Li PDHB-AS suppresses cervical cancer progression and cisplatin resistance via inhibition on Wnt/β-catenin pathway Cell Death and Disease |
| title | PDHB-AS suppresses cervical cancer progression and cisplatin resistance via inhibition on Wnt/β-catenin pathway |
| title_full | PDHB-AS suppresses cervical cancer progression and cisplatin resistance via inhibition on Wnt/β-catenin pathway |
| title_fullStr | PDHB-AS suppresses cervical cancer progression and cisplatin resistance via inhibition on Wnt/β-catenin pathway |
| title_full_unstemmed | PDHB-AS suppresses cervical cancer progression and cisplatin resistance via inhibition on Wnt/β-catenin pathway |
| title_short | PDHB-AS suppresses cervical cancer progression and cisplatin resistance via inhibition on Wnt/β-catenin pathway |
| title_sort | pdhb as suppresses cervical cancer progression and cisplatin resistance via inhibition on wnt β catenin pathway |
| url | https://doi.org/10.1038/s41419-022-05547-5 |
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