Biochemical and Biophysical Research Communications
FAM60A, increased by Helicobacter pylori, promotes proliferation and suppresses apoptosis of gastric cancer cells by targeting the PI3K/AKT pathway
Introduction
Gastric cancer (GC) has been the second fatal disease in the world [1,2]. Despite multiple therapies, the prognosis of GC remains very poor. Helicobacter pylori infection has been especially one of the most critical factors of GC. However, the mechanism for how H.pylori promotes GC remains unclear [3].
FAM60A is a protein that exists in SIN3/HDAC deacetylase complex. The role of FAM60A in the SIN3/HDAC deacetylase complex is not clear. It’ s found that the highest levels of FAM60A present in lung cancer (A549), and pancreatic cancer (Capan-2) cell lines [4]. In the esophageal cancer cells, FAM60A can promote proliferation and metastasis, playing the role of an oncogene [5].
There has been no study to explore the expression and the biological function of FAM60A in gastric cancer tissues or cell lines. We searched Oncomine and TCGA databases and found a difference in the levels of FAM60A between gastric cancer and adjacent tissues. Moreover, according to the microarray data in the study of Marios Giannakis Et al. in GEO, the mRNA levels of fam60a significantly increased in the mouse gastric epithelial cell lines after infected by H. pylori [6].
In this study, we examined the effect of H. pylori infection on FAM60A and the subsequent biological impact on gastric cancer cells. We found that H. pylori infection causes upregulation of FAM60A in gastric cancer cells, leading to proliferation. These results provide a new perspective on the mechanism of how H.pylori promotes GC.
Section snippets
Bioinformatic mining methods
We searched the cancer-associated public databases Oncomine and TCGA to predict FAM60A mRNA expression in gastric cancer and healthy gastric tissue. The relationship between FAM60A expression and overall survival (OS) was analyzed and plotted in the Kaplan-Meier database (http://kmplot.com). The median FAM60A expression was used as the cutoff. Hazard ratios with 95% confidence intervals and log-rank P values were calculated.
Tissue samples and patient clinical information
This study enrolled a total of 42 patients diagnosed with gastric
FAM60A expression levels in gastric cancer are upregulated and associated with poor prognosis
Oncomine database was used to examine the differential expression levels of FAM60A between gastric cancer and healthy gastric tissues. The FAM60A mRNA expression level was dramatically higher in cancer tissues, especially in gastric intestinal-type adenocarcinoma (Fig. 1A–C).
To confirm, we performed immunohistochemistry assay to compare FAM60A protein levels in GC tissues from 42 cases with those in the matched adjacent tissues. The immunoreactive score in gastric cancer tissues was
Discussion
FAM60A, firstly described by Smith, K. T. in 2012, exists in SIN3/HDAC deacetylase complex [4]. Although the SIN3/HDAC deacetylase complex deacetylates histone proteins,the function of FAM60A in the complex is not clear [[8], [9], [10]]. As for cancers, similar to SIN3, FAM60A can act as an oncogene or a tumor suppressor, depending on the context [[11], [12], [13]]. It’ s found that FAM60A protein presents the highest levels in lung cancer cell lines(A549), and pancreatic cancer cell
Acknowledgment
Funding for department construction in 2017, China Medical University, China. ID: 3110117038.
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