IFIT2 Depletion Promotes Cancer Stem Cell-like Phenotypes in Oral Cancer.

(1) Background: Cancer stem cells (CSCs) are a small cell population associated with chemoresistance, metastasis and increased mortality rate in oral cancer. Interferon-induced proteins with tetratricopeptide repeats 2 (IFIT2) depletion results in epithelial to mesenchymal transition, invasion, metastasis, and chemoresistance in oral cancer. To date, no study has demonstrated the effect of IFIT2 depletion on the CSC-like phenotype in oral cancer cells. (2) Methods: Q-PCR, sphere formation, Hoechst 33,342 dye exclusion, immunofluorescence staining, and flow cytometry assays were performed to evaluate the expression of the CSC markers in IFIT2-depleted cells. A tumorigenicity assay was adopted to assess the tumor formation ability. Immunohistochemical staining was used to examine the protein levels of IFIT2 and CD24 in oral cancer patients. (3) Results: The cultured IFIT2 knockdown cells exhibited an overexpression of ABCG2 and CD44 and a downregulation of CD24 and gave rise to CSC-like phenotypes. Clinically, there was a positive correlation between IFIT2 and CD24 in the patients. IFIT2high/CD24high/CD44low expression profiles predicted a better prognosis in HNC, including oral cancer. The TNF-α blockade abolished the IFIT2 depletion-induced sphere formation, indicating that TNF-α may be involved in the CSC-like phenotypes in oral cancer. (4) Conclusions: The present study demonstrates that IFIT2 depletion promotes CSC-like phenotypes in oral cancer.

Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors.

Tick-borne encephalitis virus (TBEV), the most medically relevant tick-transmitted flavivirus in Eurasia, targets the host central nervous system and frequently causes severe encephalitis. The severity of TBEV-induced neuropathogenesis is highly cell-type specific and the exact mechanism responsible for such differences has not been fully described yet. Thus, we performed a comprehensive analysis of alterations in host poly-(A)/miRNA/lncRNA expression upon TBEV infection in vitro in human primary neurons (high cytopathic effect) and astrocytes (low cytopathic effect). Infection with severe but not mild TBEV strain resulted in a high neuronal death rate. In comparison, infection with either of TBEV strains in human astrocytes did not. Differential expression and splicing analyses with an in silico prediction of miRNA/mRNA/lncRNA/vd-sRNA networks found significant changes in inflammatory and immune response pathways, nervous system development and regulation of mitosis in TBEV Hypr-infected neurons. Candidate mechanisms responsible for the aforementioned phenomena include specific regulation of host mRNA levels via differentially expressed miRNAs/lncRNAs or vd-sRNAs mimicking endogenous miRNAs and virus-driven modulation of host pre-mRNA splicing. We suggest that these factors are responsible for the observed differences in the virulence manifestation of both TBEV strains in different cell lines. This work brings the first complex overview of alterations in the transcriptome of human astrocytes and neurons during the infection by two TBEV strains of different virulence. The resulting data could serve as a starting point for further studies dealing with the mechanism of TBEV-host interactions and the related processes of TBEV pathogenesis.

Clinical significance of IFIT2 expression in human renal cancer tissues.

BACKGROUND: Interferon (IFN)-induced protein with tetratricopeptide repeats 2 (IFIT2) is an important member of the IFN-stimulated gene (ISG) family. It has been demonstrated that IFIT2 is important in the physiopathological processes of antiviral and antitumor activities. We previously demonstrated that IFIT2 was highly expressed in paracarcinoma tissues compared with gastric cancer tissues, and its expression level was positively correlated with a superior postoperative prognosis of the patients. METHODS: We performed immunohistochemical staining of IFIT2 in human clear cell renal cell carcinoma (ccRCC) tissues by using a tissue microarray. RNAseq data of kidney clear cell carcinoma (KIRC) samples from The Cancer Genome Atlas (TCGA) were used to perform the enrichment analyses based on the genes that were highly correlated with IFIT2. RESULTS: Weak staining of IFIT2 was located on the cytoplasm and cell membrane surface of the cancer cells, while positive staining of IFIT2 was located mainly on adjacent normal tissues. Survival analysis showed that patients with higher IFIT2 expression had better overall survival than patients with lower IFIT2 expression (P=0.030). The Cox model further demonstrated that age (P=0.002), pathological stage (P=0.000), TNM stage (P=0.005) and IFIT2 expression (P=0.003) could be used as independent prognostic predictors for ccRCC patients. Additionally, the enrichment analysis based on ccRCC expression profile data extracted from TCGA revealed that the genes highly correlated with IFIT2 were mainly related to the biological processes of virus response, T cells and the innate immune response (GO:0009615, GO:0042110, and GO:0045088) and the pathways of NLR signaling, chemokine signaling, and TLR signaling (hsa04621, hsa04062, and hsa04620). CONCLUSIONS: IFIT2 could serve as a potential prognostic marker for ccRCC patients, and the mechanism of decreased IFIT2 expression in the progression of ccRCC merits further investigation.

Expression of interferon-induced protein with tetratricopeptide repeats 2（IFIT2） in lung cancer tissue and its clinical significance / 临床检验杂志

Objective@#To investigate the expression of IFIT2 (interferon-induced protein with tetratricopeptide repeats 2) in human lung cancer tissue and analyze the relationship between the IFIT2 expression and clinicopathological features and prognosis. @*Methods@#Tissue microarray and immunofluorescence staining were used to examine the IFIT2 expression in lung cancer tissue and their adjacent tissues. Wilcoxon rank test was used to compare the IFIT2 expression in lung cancer and corresponding adjacent tissues. The chi-square test was used to analyze the relationship between the IFIT2 expression in lung cancer tissues and clinicopathological features of the patients. Kaplan-Meier survival analysis was performed to analyze the correlation between IFIT2 expression and patients′ overall survival. Cox model was used to analyze the correlation between different clinical parameters and prognosis. @*Results@#There was significant difference for the IFIT2 expression between the lung cancer tissues and adjacent tissues (P＜0.01). There was no significant correlation between IFIT2 expression and clinicopathological features of patients (P＞0.05). In lung adenocarcinoma and squamous cell carcinoma, Kaplan-Merier survival analysis showed that the overall survival (OS) of patients in IFIT2 low expression group was significantly shorter than that in IFIT2 high expression group (HR=2.392, 95%CI: 1.103-5.186, P=0.027; HR=2.907, 95%CI: 1.118-7.559, P=0.029, respectively). Multi-factor Cox model analysis indicated that distant metastasis (HR=8.033, 95% CI: 3.664-17.614, P=0.000) was independent prognostic factors for lung adenocarcinoma, lymph node metastasis (HR=3.390, 95% CI: 1.029-11.175, P=0.045) and IFIT2 low expression (HR=3.762,95%CI: 1.236-11.451, P=0.020) were independent prognostic factors for lung squamous cell carcinoma. @*Conclusion@#The down-regulated expression of IFIT2 in lung cancer tissues suggests that it may play an important role in initiation and development of lung cancer. It could be used as a valuable risk factor to predict the prognosis of lung cancer patients.