Fat mass and obesity-associated protein promotes the tumorigenesis and development of liver cancer

Abstract

Liver cancer is the fourth leading cause of cancer-associated mortality worldwide. Statistics indicate that the incidence of liver cancer has been increasing and that its prognosis remains poor. Fat mass and obesity-associated protein (FTO) is a demethylase that is involved in N6-methyladenosine (m6a) RNA modification; however, to the best of our knowledge, its role in tumorigenesis and development of liver cancer remains unknown. In the present study, cell proliferation, colony formation, apoptosis, Transwell and wound healing assays of small interfering (si)RNA-FTO HepG2 cells were performed, and the levels of m6A RNA methylation were assessed. Additionally, the prognostic value of FTO in liver cancer was analyzed using immunohistochemistry analysis. The results from the EpiQuik m6A RNA methylation quantitative assay revealed that knockdown of FTO increased the total m6A methylation level. Notably, FTO promoted the proliferation and migration of liver cancer cells. Additionally, FTO expression was upregulated in patients with liver cancer and was associated with a high Edmondson Grade, which served as an independent prognostic factor for liver cancer. Results from the Kaplan-Meier survival analysis revealed that low expression levels of FTO predicted a good prognosis. The 5-year overall survival of the low FTO expression group was 68% compared with 48% in the high FTO expression group (P=0.077). In conclusion, the present study suggested that FTO regulates the tumorigenesis and development of liver cancer.

RNA m6A methylation regulators in liver cancer

“…It suggests that it may promote the proliferation and migration of hepatoma cells. In addition, upregulation of FTO expression in patients with liver cancer is associated with high Edmondson grade, which is an independent prognostic factor for liver cancer [ 87 ]. The study by Zhao et al showed that patients with decreased FTO expression had shorter overall survival and tumor-free survival compared with patients with normal FTO expression [ 88 ].…”

Associations of DDX60L With the Clinical Features and Prognosis of Hepatocellular Carcinoma

“…Subsequently, tissue microarray slices were incubated for 16 h at 4°C with the primary antibody against DDX60L (dilution, 1:400; catalog number bs-14236R; Beijing Biosynthesis Biotechnology Co., Ltd.), followed by incubation with EnVision+ System-HRP (catalog number K4001, Dako). Finally, the staining was visualized with the DAB Substrate kit (catalog number DA1010-2, Solarbio) and counterstained with hematoxylin (22).…”

“…The staining intensity was assessed using a fourgrade grading system: 3 (strong), 2 (moderate), 1 (weak), and 0 (negative). The percentage of DDX60L-positive cells was scored as follows: 0 (less than 5%), 1 (6-25%), 2 (26-50%), 3 (51-75%), and 4 (>75%) (22). The staining intensity scores and the percentage of positive cells were multiplied to obtain the final immunohistochemical staining score of DDX60L.…”

Emerging Roles of N6-Methyladenosine Demethylases and Its Interaction with Environmental Toxicants in Digestive System Cancers

“…Several studies hold conflicting opinions against above results, suggesting that FTO was overexpressed in HCC and could promote proliferation and invasion. 47 , 48 According to a long-term mice experiment, FTO is essential for the control of energy balance and glucose metabolism. Importantly, during the initiation phase of tumor development, FTO is upregulated on acute liver damage but plays protective roles in HCC development.…”