Combination of IFITM1 knockdown and radiotherapy inhibits the growth of oral cancer

Abstract

This research aimed to analyze the effect of IFITM1 on the radioresistance of oral neoplasm. Using a multi‐group heat map from GSE9716 analysis of the GEO database, IFITM1 was determined to be a relevant radioresistance gene. The TCGA database was analyzed before the expression of IFITM1 was analyzed. IFITM1 expression was quantified by quantitative RT‐PCR and immunohistochemistry in 19 paired oral neoplasm cases. The effects of time and dose of radiation on IFITM1 expression level in CAL27 and TSCC1 cell lines were tested by quantitative RT‐PCR. Oral neoplasm cells were transfected with siRNA after radiotherapy to disturb IFITM1 expression. After this, the survival rates, cell apoptosis, caspase‐3 viability, expression and γ‐H2AX were detected using colony formation, flow cytometry, western blot and immunofluorescence, respectively. Western blot was used for STAT1/2/3/p21‐related protein and phosphorylation changes. Finally, an in vivo nude mice tumor model was established to verify the effect of IFITM1 on oral neoplasm cells radioresistance. Through microarray analysis, the head and neck neoplasm radioresistance‐related gene IFITM1 was found to be overexpressed. IFITM1 overexpression was verified not only using the TCGA database but also in 19 paired cases of oral neoplasm tissues and cells. With increases of dose and time of radiation, the expression of IFITM1 was increased in CAL27 and TSCC1 cell lines. Furthermore, si‐IFITM1 may restrain cell proliferation, DNA damage and cell apoptosis in oral neoplasm cell lines. Finally, pSTAT1/2/p21 was found to be upregulated while pSTAT3/p‐p21 was downregulated due to IFITM1 inhibition after radiotherapy. The evidence suggested that IFITM1 in combination with radiotherapy can inhibit oral neoplasm cells.

The double face of miR-320: cardiomyocytes-derived miR-320 deteriorated while fibroblasts-derived miR-320 protected against heart failure induced by transverse aortic constriction

“… 40 Meanwhile, some studies indicated that IFITM1 played a key role in the radio-resistance of oral neoplasm through the pSTAT3/p-p21 pathway. 41 PLEKHM3 could potentially function as a scaffold protein for PKB during differentiation through PI3K signaling cascade. 42 In the current study, we found that miR-320 inhibited IFITM1 expression in CFs and target PLEKHM3 in CMs, which was involved in the process of cardiac remodeling.…”

The Therapeutic Potential of Adipose Tissue-Derived Mesenchymal Stem Cells to Enhance Radiotherapy Effects on Hepatocellular Carcinoma

“…STAT3 is considered to promote formation of many tumors including HCC, and the mutual interplay between STAT3, caspases and MMPs and IFITM1 was revealed by Meng et al (Eferl, 2012). More recently, IFITM1 was identified as a radioresistance gene by analysis of the GEO database and verified by diverse experiments (Yang J. et al, 2018). It has been suggested that the combination of IFITM1 knockdown with RT inhibited oral neoplasms.…”

“…Markov cluster algorithm (MCL) was applied to generate modules, by applying the size ≥3 as a cutoff to filter out network (Figure 5D) To evaluate which of these RNAs may be related to the synergistic effects of the combination treatment, we performed a validation analysis using the NCBI Gene database to determine whether the sequence matched to that of a human RNA sequence, and also conducted a comprehensive literature search of the genes in relation to carcinogenesis to identify the biological functions of each gene. Based on the average log2 ratio values and previous studies (Gao et al, 2015; Lui et al, 2017; Yang J. et al, 2018), the RNA IFITM1 gene, which was downregulated in RTM group, was selected for analysis in further experiments after confirmed in vitro experiment (Figure 6B). We performed Western blot, qRT-PCR and IHC analyses on mouse tumors, and found decreased IFITM1 expression in RTM group compared to other groups (Figures 5E–H).…”

The Identification and Validation of a Robust Immune-Associated Gene Signature in Cutaneous Melanoma

“…Journal of Immunology Research peripheral nervous system and was linked with the increasing rate of metastasis and death [45,46]. IFITM1 was reported to participate in the signals of cell adhesion and antiproliferation transduction [47]. And the overexpression of IFITM1 was confirmed to be correlated with the progressing of several cancers including ovarian cancer, breast cancer, oral cancer, lymphoma, and leukemia [48].…”