<p>CHFR promotes the migration of human gastric cancer cells by inducing epithelial-to-mesenchymal transition in a HDAC1-dependent manner</p>

Abstract

BackgroundPrevious studies have illustrated that checkpoint with forkhead-associated and ring finger domains (CHFR) was frequently silenced in several cancer types due to promoter hypermethylation and functions as a tumor suppressor gene. However, the data from the public dataset reveal that CHFR is highly expressed in human gastric cancer specimens, and the biological function of CHFR in gastric cancer is still not well understood.Materials and methodsThe clinical association between CHFR expression and the overall survival of gastric cancer patients as well as cancer metastasis was analyzed according to public datasets. The CHFR expression in clinical specimens and human gastric cancer cell lines was detected by immunohistochemistry and Western blotting, respectively. Gain (overexpression) and loss (silencing) of function experiments were used to elucidate the role of CHFR in gastric cancer. The migration ability of gastric cancer cells was determined by wound healing and transwell assays. Cell cycle distribution was analyzed using fluorescence-activated cell sorting experiment. The expression of the proteins in cancer cells was measured using Western blot analysis.ResultsAccording to the analysis from Kaplan–Meier plotter dataset, CHFR expression was negatively associated with overall survival of gastric cancer patients. Our data revealed that exogenous expression of CHFR not only arrested cell cycle but also led to dramatically enhanced cell migration, while silencing of CHFR significantly inhibited cell migration in gastric cancer cells. This result is consistent with the data from the Human Cancer Metastasis Dataset, in which CHFR level is found to significantly increase in metastatic gastric cancer. The overexpression of CHFR promoted epithelial–mesenchymal transition (EMT) in both SGC-7901 and AGS cells, while HDAC1 was inhibited. Interestingly, suberoylanilide hydroxamic acid, a HDAC1 antagonist, could effectively increase cell migration in both cell lines via enhancement of EMT.ConclusionOur data indicated that CHFR exerted positive effects on cell migration of human gastric cancer by promoting EMT via downregulating HDAC1.

Expression of lipid transport‐associated genes in lipid‐deprived cancer cells

“…On the other hand, at the 24‐hr time‐point, many genes were consistently upregulated in at least four cell lines. Table 1 displays the list of these genes, the information on family, molecular function ligands (lipid transport‐associated), subcellular localization, and cancer‐associated expression patterns of their encoded proteins are also provided (Carrara et al., 2018; Chen et al., 2020; Esau et al., 2016; Gordon et al., 2019; D. Jiang et al., 2020; Koochekpour et al., 2007; Swanton et al., 2007; Thorsen et al., 2011; Verma et al., 2020; Yang, He, et al., 2019; M. Zhang, Xiang, et al., 2020; Zheng et al., 2018). It was observed that STARD4, OSBPL9 LDLR, and SCARB1 genes were significantly upregulated in all the LPDS‐treated (24 hr) cell lines, whereas CERT1, OSBPL5, OSBPL1A, APOLD1, APOL5, CTEP, PSAP, CFHR4, APOO, and SLC27A6 were upregulated in at least four of the five cell lines (Table 1 and Figure 2).…”

“…Table 1 displays the list of these genes, the information on family, molecular function ligands (lipid transport-associated), subcellular localization, and cancer-associated expression patterns of their encoded proteins are also provided (Carrara et al, 2018;Chen et al, 2020;Esau et al, 2016;Gordon et al, 2019;D. Jiang et al, 2020;Koochekpour et al, 2007;Swanton et al, 2007;Thorsen et al, 2011;Verma et al, 2020;Yang, He, et al, 2019;M. Zhang, Xiang, et al, 2020;Zheng et al, 2018).…”

Suppression of histone deacetylase 1 by JSL-1 attenuates the progression and metastasis of cholangiocarcinoma via the TPX2/Snail axis

“…For example, HDAC1 has been demonstrated to be tumor promoter in a range of malignancies, covering gastrointestinal tumors such as colorectal cancer [ 18 ], and gastric cancer [ 19 ], as well as HCC [ 20 ] and ovarian cancer [ 21 ]. Inhibition of this HDAC has recently been corroborated to prevent the progression of gastric cancer [ 22 ] and esophageal carcinoma [ 23 ]. The major results from the present study revealed that HDAC1 was highly expressed in CC clinical samples and cells, whereas shRNA-induced silencing of HDAC1 contributed to prevention against CC progression, supported by the restrained proliferative, migratory and invasive capabilities of CC cells.…”

Development of an Individualized Ubiquitin Prognostic Signature for Clear Cell Renal Cell Carcinoma

“…Numerous studies have shown that the CHFR gene is significantly silenced or mutated by promoter methylation in many cancer types including nonsmall cell lung cancer (Mizuno et al, 2002) and esophageal cancer (Shibata et al, 2002). Yang et al (2019) found that CHFR promoted the invasion of gastric cancer cells by inducing epithelial to mesenchymal transformation in a HDAC1dependent manner. Coronin-6, a gene product of CORO6, is a member of the coronin family and has been shown to play a role in cell movement, vesicle transport, and cell division (Roadcap et al, 2008).…”