The m 6 A eraser FTO facilitates proliferation and migration of human cervical cancer cells
- PDF / 9,753,410 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 104 Downloads / 179 Views
Cancer Cell International Open Access
PRIMARY RESEARCH
The m6A eraser FTO facilitates proliferation and migration of human cervical cancer cells Dongling Zou1* , Lei Dong2, Chenying Li3, Zhe Yin1, Shuan Rao4* and Qi Zhou1*
Abstract Background: Since FTO was recognized as the first m6A demethylase, the understanding of its biological function has been widely expanded. However, the role of FTO in cervical cancer tumorigenesis remains unclear. Methods: In this study, we first analyzed the expression of FTO in two independent human cancer datasets and evaluated the correlation between FTO level and cervical cancer progression. Using small hairpin RNA technology, we explored the function of FTO in cervical cancer cell line Hela and SiHa cells, respectively. We then determined the FTO targets by performing transcriptional profile with FTO deficient and competent Hela cells, and finally validated these targets with ribosome profiling and functional rescue experiments. Results: Our data suggested that FTO was frequently overexpressed in human cervical cancer tissues and highly correlated with cervical cancer progression. FTO serves as an oncogenic regulator for cervical cancer cells’ proliferation and migration which is vastly depended on its demethylase activity. Mechanistically, FTO interacts with transcripts of E2F1 and Myc, inhibition of FTO significantly impairs the translation efficiency of E2F1 and Myc, however, either overexpress E2F1 or Myc sufficiently compensates the FTO deficiency which decreases cell proliferation and migration. Conclusions: Our study indicates that FTO plays important oncogenic role in regulating cervical cancer cells’ proliferation and migration via controlling m6A modification of E2F1 and Myc transcripts. FTO represents a potential drug candidate for cervical cancer therapy. Keywords: FTO, m6A, Demethylase, E2F1, Myc, Translation Background Cervical cancer is one of the most prevalent gynecological cancer worldwide, ranking 4th among all female cancers and affects about 450,000 newly diagnosed cases every year [1, 2]. Despite the advances in the screening and early prevention of cervical cancer dramatically decreases the overall cervical cancer incidence and mortality in United States and other western countries [3], a vast majority of patients in low and low-middle income countries are still diagnosed as locally advanced *Correspondence: [email protected]; [email protected]; [email protected] 1 Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing 400030, China 4 Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China Full list of author information is available at the end of the article
or invasive cervical cancer with high risks of morbidity, metastasis as well as recurrence [4]. Therefore, it is necessary to seek novel biomarkers for early detection and new targets for impro
Data Loading...
