Affiliation:
1. Department of Obstetrics and Gynecology, West China Second University Hospital Sichuan University Chengdu Sichuan China
2. The Key Laboratory of Birth Defects and Related Diseases of Women and Children (West China Second University Hospital Sichuan University), Ministry of Education Chengdu Sichuan China
Abstract
AbstractThe long noncoding RNA PVT1 is reported to act as an oncogene in several kinds of cancers, especially ovarian cancer (OV). Abnormal levels of N6‐methyladenosine, a dynamic and reversible modification, are associated with tumorigenesis and malignancies. Our previous study reported that PVT1 plays critical roles in regulating OV. However, it is still largely unknown how m6A modification affects OV via PVT1. In this study, we aimed to investigate the regulation of ALKBH5 by affecting PVT1 in OV. We first found that the PVT1 RNA level was higher in OV cells than in IOSE80 cells, and conversely, the m6A modification level of PVT1 was lower in OV cells. By searching the HPA, ALKBH5, which is responsible for PVT1 demethylation, was found to be upregulated in OV tissues versus normal ovarian tissues. ALKBH5 binds to PVT1 RNA, and knockdown of ALKBH5 decreased PVT1 RNA levels. ALKBH5 also increased FOXM1 levels by upregulating PVT1, at least partially. Knockdown of ALKBH5 suppressed OV growth, colony formation, tumour formation and invasion, which were partially reversed by overexpression of PVT1. Moreover, ALKBH5 knockdown decreased FOXM1 levels by regulating PVT1 RNA expression, subsequently increasing the sensitivity to carboplatin, 5‐FU and docetaxel chemotherapy. Taken together, these results indicate that ALKBH5 directly regulates the m6A modification and stability of PVT1. Then, modified PVT1 further regulates FOXM1 and thus affects malignant behaviours and chemosensitivity in OV cells. All these results indicate that ALKBH5 regulates the malignant behaviour of OV by regulating PVT1/FOXM1.
Subject
Cell Biology,Molecular Medicine
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献