YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells
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RESEARCH
Open Access
YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells Jie Li1* , Lei Wu2, Meili Pei2 and Yun Zhang1
Abstract RNA methylation can reverse the methylation modification at the RNA level, which is an extremely important epigenetic modification. The function and mechanism of YTHDF2, as a reader of m6A modification, in epithelial ovarian cancer (EOC) have not been elucidated so far. This study aimed to investigate how YTHDF2 and miR-145 modulated EOC progression through m6A modification. It demonstrated that YTHDF2 was significantly upregulated in EOC tissues compared with normal ovarian tissues. Further functional studies confirmed that YTHDF2 significantly promoted the proliferation and migration of EOC cell lines and reduced the global 6-methyladenine (m6A) mRNA levels. Next, the expression levels of miR-145 and YTHDF2 were found to be inversely correlated in ovarian cancer tissues and cells, and YTHDF2 was the direct target gene of miR-145. A crucial crosstalk occurred between miR-145 and YTHDF2 via a doublenegative feedback loop. The overexpression of YTHDF2 rescued miR-145-induced reduction of the proliferation and migration of EOC cells. Hence, YTHDF2 and miR-145, as two crucial m6A regulators, were involved in the progression of EOC by indirectly modulating m6A levels. The findings of this study on YTHDF2 and miR-145 might provide new insights into carcinogenesis and new potential therapeutic targets for EOC. Keywords: YTHDF2, m6A, miR-145, Ovarian cancer
Introduction Ovarian cancer is a common malignant tumor of the female reproductive system, and its mortality rate ranks first among gynecological tumors [1]. It has many histopathological types, about 90% of which belong to epithelial ovarian cancer (EOC). Patients with EOC have no obvious symptoms and signs in the early stage and lack effective means of early screening. Consequently, most of them reach the late stage before a clear diagnosis. The main treatment of EOC is surgery, supplemented by intravenous chemotherapy or intraperitoneal perfusion chemotherapy or combination therapy. However, the treatment has not achieved satisfactory results; the 5* Correspondence: [email protected] 1 Department of Pathology, the First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Road, Xi’an 710061, Shaanxi, China Full list of author information is available at the end of the article
year survival rate of patients with EOC is still around 40% [2]. Besides the difficulty in early diagnosis, the poor prognosis of patients is also attributed to tumor recurrence and metastasis [3]. Therefore, early sensitive markers of EOC should be discovered, key molecules related to EOC recurrence and metastasis should be identified, and a targeted and multi-functional gene therapy should be developed on an urgent basis. RNA methylation can reverse the methylation modification at the RNA level, which is an extremely important epigenetic modification [4]. Further, 6-methyladenine (m6A) is
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