Decreased IFIT2 Expression Promotes Gastric Cancer Progression and Predicts Poor Prognosis of the Patients

Abstract

Background/Aims: The status of interferon (IFN) signaling pathway has been shown to be closely associated with the response of immune checkpoint blockade therapy against advanced human cancers. IFN-induced protein with tetratricopeptide repeats 2 (IFIT2), also known as IFN-stimulated gene 54 (ISG54), is one of the most highly responsive ISGs, which can inhibit the proliferation and migration of cancer cells, and regulate viral replication, resulting in anti-cancer and anti-viral effects. In the present study, we aimed to investigate the role of IFIT2 in human gastric cancer. Methods: Immunohistochemistry assay was used to investigate the correlation between the IFIT2 expression in cancer tissues and clinical parameters of gastric cancer patients. Knockdown of IFIT2 was performed using RNAi to assess the role of IFIT2 in the regulation of biological behaviors in human gastric cancer cell lines. Results: IFIT2 expression in gastric cancer tissues was significantly associated with tumor stage and postoperative prognoses of the patients. Moreover, decreased IFIT2 expression in human gastric cancer cell lines SGC-7901 and AGS significantly increased the cell viability, cell migration and the ratios of cells in S phase. Conclusion: Our present study demonstrated that the decreased IFIT2 expression could promote the gastric cancer progression and predict poor therapeutic outcomes of the patients.

Expression of B7-H6 expression in human hepatocellular carcinoma and its clinical significance

“…Immunohistochemical staining was performed as described in our previous reports [12–15]. Briefly, the HCC tissue array block was cut into 4-µm-thick sections, and the sections were dewaxed in xylene and rehydrated in a graded series of alcohols.…”

“…Cell migration ability was assessed using a wound scrape assay to examine the role of B7-H6 in regulating the migration ability of HCC cell lines, as described in our previous studies [12, 17, 18]. Briefly, cells from the LV-B7-H6-shRNA and LV-NC groups were maintained in 6-well plates.…”

“…The Transwell culture system was used to examine the invasive ability of the HCC cell lines after knockdown of B7-H6 expression, as described in our previous studies [12, 17, 18]. Briefly, the upper chamber of Transwell ® inserts with a pore size of 8 μm and a diameter of 6.5 mm was coated with 20 μL of Matrigel (diluted 1:3 in serum-free DMEM) and was incubated at 37 °C for 4 h. Cells from the LV-B7-H6-shRNA and LV-NC groups were harvested by trypsinization after 12 h of serum starvation and were then resuspended in a serum-free DMEM at a density of 1 × 10 6  cells/mL.…”

Emerging Functions of Human IFIT Proteins in Cancer

“…Although IFITs are involved in the host immune response and antiviral defense, emerging research studies have shown their involvement in malignant progression (Lai et al, 2008(Lai et al, , 2013Niess et al, 2015;Zhang et al, 2016;Ohsugi et al, 2017;Yang et al, 2017;Zhao et al, 2017;Chen et al, 2018;Lo et al, 2018Lo et al, , 2019Nushtaeva et al, 2018;Shen et al, 2018;Huang et al, 2019). The epithelial-mesenchymal transition (EMT) is a biological mechanism in which epithelial cells convert into a mesenchymal phenotype to acquire increased cell invasion and migration capacity as well as resistance to apoptosis (Kalluri and Weinberg, 2009), which lead to metastasis (Yilmaz and Christofori, 2009).…”

“…In contrast, IFIT2 has been shown to have tumor suppressor function in many cancers. Decreased expression of IFIT2 is associated with increased cell proliferation and metastasis and predicts poor clinical outcome in gastric cancer patients (Chen et al, 2018). Downregulation of IFIT2 expression was observed in colorectal cancer (CRC) tissues compared to normal tissues.…”