FTO expression is associated with the occurrence of gastric cancer and prognosis

Abstract

Fat mass and obesity associated (FTO) is a protein-coding gene. FTO gene is an obesity related gene, also known as the obesity gene. It has been reported previously that FTO is associated with a variety of malignant cancers, such as breast, thyroid and endometrial cancer. The aim of the present study was investigate the FTO expression of human gastric cancer and to investigate its clinical value. FTO expression was determined by immunohistochemical analysis with tissue microarrays in GC tissues and corresponding adjacent non-tumor tissues. Moreover, the results in protein and mRNA level were confirmed by the real-time PCR and western blot analysis. The relationship between the FTO expression and the pathological characteristics of GC patients was also explored. In addition, by using MTT, clone formation and transwell assays, we studied the effects of FTO expression on biological function of GC cells in vitro. The Kaplan-Meier method and the log-rank test were used to compare the overall survival rate between the FTO high-expression group and the low-expression group. We affirmed repeatedly upregulation of FTO expression in both protein and mRNA levels in GC tissues compared to corresponding adjacent non-tumor tissues. Immunohistochemistry by tissue microarray of FTO expression was remarkably increased in GC tissues (72 of 128, 56.3%) compared with adjacent non-tumor tissues (24 of 62, 38.7%). FTO expression level was closely related to low differentiation (P<0.001), lymph node metastasis (P=0.029). The expression of FTO was positively correlated with TNM stage (P<0.001). the Kaplan-Meier analysis showed that high FTO expression was significantly associated with poor prognosis in GC patients. Downregulation of FTO expression significantly inhibited the proliferation, migration and invasion of GC cell lines. On the contrary, overexpression of FTO promoted the proliferation, migration and invasion of GC cell lines. This study indicates that FTO expression may have an important role in promoting the occurrence of GC, and it may be an vital molecular marker in the diagnosis and prognosis of GC patients.

<p>FTO Facilitates Lung Adenocarcinoma Cell Progression by Activating Cell Migration Through mRNA Demethylation</p>

“…24 However, other studies drew a contrasting conclusion and indicated that FTO promotes the proliferation, migration, and invasion of GC cell lines. 16 Numerous studies have indicated that high FTO expression is significantly associated with cancer development. FTO enhances LUSC proliferation and invasion by reducing m6A levels and mRNA stability in myeloid zinc finger 1 (MZF1) mRNA transcription.…”

“…17 The FTO expression level is closely related to low levels of differentiation and lymph node metastasis in GC; FTO overexpression promotes the proliferation, migration, and invasion of GC cell lines. 16 In cervical cancer, upregulated FTO represses the m6A modification of β-catenin and induces chemoradiotherapy resistance. 18 Elevated FTO leads to a low level of m6A modification of the untranslated regions of ankyrin repeat and SOCS box protein 2 and retinoic acid receptor alpha, thus reducing the mRNA and protein levels of these anti-angiogenic genes; C21orf59, MZF1, and taxilin alpha oncogene expression levels then increase, leading to the promotion of acute myeloid leukemia.…”

“…14 In addition, FTO overexpression has been indicated in various cancers, including LUSC, NSCLC, gastric cancer (GC), cervical carcinoma, pancreatic cancer, and acute myeloid leukemia. [14][15][16][17][18][19] FTO is strongly associated with various cancers, but limited knowledge on the role of FTO in LUAC is available.…”

Human and Arabidopsis alpha‐ketoglutarate‐dependent dioxygenase homolog proteins—New players in important regulatory processes

“…In melanoma, tumorigenesis is caused by specific demethylation of mRNA of programmmed cell death protein 1, C‐X‐C chemokine receptor 4, and transcription factor SOX‐10. Moreover, for AML, gastric, endometrial, or HNSCC, this protein is involved in cancer development . An elevated FTO level is also responsible for chemotherapy resistance of cervical squamous cell carcinoma (Figure ).…”

The Butterfly Effect of RNA Alterations on Transcriptomic Equilibrium

“…Another well-studied regulator of RNA methylation is fat mass and obesity-associated protein (FTO), which removes the m6A mark from mRNAs [100]. Increased expression of FTO enhances tumorigenesis of breast cancer as well as acute myeloid leukemia (AML), and is associated with poor prognosis of gastric cancer patients [101][102][103]. Recent efforts have focused on the development of therapies targeting the m6A reader YTHDF2, which selectively inhibits the growth of leukemic stem cells without affecting the proliferation of hematopoietic stem cells in a mouse model of AML [104].…”