CXCR3, belonging to CXC chemokine receptors, has been identified to be overexpressed in various kinds of tumors. There are three mRNA variants of CXCR3 (CXCR3A, CXCR3B and CXCR3alt) in human cells. The functions of major CXCR3 isoforms (CXCR3A, CXCR3B) have been reported in some tumors including prostate and breast cancer. However, the effects of CXCR3A and CXCR3B on gastric cancer cell progression remain unknown. The present investigation found that CXCR3A mRNA level was upregulated but CXCR3B mRNA level was downregulated in gastric cancer cells and tissues. In vitro growth analysis showed that CXCR3A acted as a positive mediator in regulating cell growth, whereas CXCR3B exerted the opposite effect. In vitro invasion and migration assays showed that CXCL10 promoted gastric cancer cell invasion and migration via CXCR3A, but not CXCR3B. Moreover, knockdown of CXCR3A inhibited cell growth and metastasis in vivo. Additionally, CXCR3A knockdown attenuated matrix metalloproteinase (MMP)‑13 and IL‑6 expression, and reduced ERK1/2 activation. Together, these data suggest that CXCR3A contributes to the growth, invasion and metastasis of gastric cancer cells in vitro and in vivo, and thus may be a key mediator of gastric cancer progression.

(-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, could affect carcinogenesis and development of many cancers. However, the effects and underlying mechanisms of EGCG on gastric cancer remain unclear. We found that EGCG significantly inhibited proliferation and increased apoptosis of SGC-7901 cells in vitro. The decreased expressions of p-β-catenin(Ser552), p-GSK3β(S9) and β-catenin target genes were detected in SGC-7901 cells after treated by EGCG. XAV939 and β-catenin plasmid were further used to demonstrate the inhibition of EGCG on canonical Wnt/β-catenin signalling. Moreover, EGCG significantly inhibited gastric tumour growth in vivo by inhibiting Wnt/β-catenin signalling. Taken together, our findings establish that EGCG suppressed gastric cancer cell proliferation and demonstrate that this inhibitory effect is related to canonical Wnt/β-catenin signalling. This study raises a new insight into gastric cancer prevention and therapy, and provides evidence that green tea could be used as a nutraceutical beverage.

Background and purpose: Homo sapiens FOXF1 adjacent noncoding developmental regulatory RNA (FENDRR) is a novel long noncoding RNA (lncRNA) exerting important effects on transcriptional and post-transcriptional regulation. The purpose of this study was to investigate the potential role of FENDRR in colon cancer. Methods: Multiple cellular and molecular biology experiments were performed in the present study, such as CCK-8, Western blot, immunohistochemistry, confocal immunofluorescent and animal studies. Results: We determined that attenuation of FENDRR was a frequent event in colon cancer tissues and colon cancer cell lines, in contrast to their normal counterparts. Low levels of FENDRR were associated with the clinical stages and poor prognosis. Moreover, ectopic expression of FENDRR repressed colon cancer cell viability, invasion and epithelial–mesenchymal transition. Furthermore, through a series of in vitro and in vivo assays, we reported the discovery of FENDRR modulating the expression of SOX4 protein, and hence in the progression of colon cancer. Conclusion: Based on these data, we demonstrated that FENDRR may function as a tumor-suppressor gene by repressing SOX4 and as a potential therapeutic target for colon cancer.

Our study desired to investigate how miR-34c-3p regulates colon cancer cell proliferation and what is the relationship between miR-34c-3p and EIF3D. HCEpiC (normal human colonic epithelial cells), SW620, HT-29, SW480, and HCT-116 (human colon cancer cells lines) were used in our study. SW620 cells were chosen and divided into blank, miR-34c-3p mimics, miR-34c-3p NC, miR-34c-3p inhibitors, Lv-EIF3D, Lv-NC, and miR-34c-3p mimics+Lv-EIF3D groups. qRT-PCR was used for the detection of miR-34c-3p and EIF3D mRNA expressions. Dual-luciferase reporter assay was performed to investigate the effect of miR-34c-3p on EIF3D. Western blot was performed to detect EIF3D, cyclin D1, and c-Myc expressions. Clone formation and MTT assay were used to measure cell proliferation ability. colon cancer cells had lower miR-34c-3p expression, but higher EIF3D expression compared with HCEpiC. EIF3D mRNA expression was regulated negatively by miR-34c-3p. In the miR-34c-3p mimics group, colon cancer cell proliferation was significantly decreased, whereas c-Myc and cyclin D1 expressions were downregulated. Colon cancer cell proliferation in miR-34c-3p inhibitors and Lv-EIF3D groups was enhanced, and c-Myc and cyclin D1 expressions were decreased. The results suggested that by targeting EIF3D, miR-34c-3p inhibited colon cancer cell proliferation.

PurposeColorectal cancer (CRC) has become a predominant cancer and accounts for approximately 10% of cancer-related mortality. Drug resistance still remains a priority mortality factor for patients due to no available therapeutic alternatives. The purpose of the present study was to investigate the underlying molecular mechanisms how eukaryotic translation initiation factor 3 subunit G (EIF3G) resensitized 5-Fu-resistant human CRC cells (HCT116/5-Fu) to 5-fluorouracil (5-Fu).MethodsMultiple cellular and molecular biology experiments were performed in the present study, such as CCK-8, western blotting and flow cytometry.ResultsWe found that EIF3G is highly expressed at RNA and protein levels in HCT116/5-Fu cells compared with HCT116 cells using quantitative real-time polymerase chain reaction and Western blot analysis. In addition, silencing EIF3G enhanced 5-Fu-induced apoptosis in HCT116/5-Fu cells. Moreover, EIF3G silencing decreased the activity of the drug-related proteins MDR1 and MRP levels in HCT116/5-Fu cells. Finally, the xenograft tumor model further confirmed that EIF3G resensitized HCT116/5-Fu tumors to 5-Fu. We observed that EIF3G silencing followed by 5-Fu administration had a synergistic interaction effect on HCT116/5-Fu in vitro and in vivo.ConclusionThese findings demonstrate that EIF3G is a targetable regulator of chemoresistance in CRC, and inhibiting EIF3G in combination with 5-Fu might be a potential therapeutic strategy for colon cancer.

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Background As EIF3D is oncogenic in colorectal cancer (CRC) and is associated with multidrug resistance, this study aims to investigate whether and how EIF3D regulates resistance to 5‐fluorouracil (5‐Fu) in CRC. Methods EIF3D‐associated genes in CRC were predicted using bioinformatics tools. CRC cells and nude mice received 5‐Fu treatment. Then, the impacts of EIF3D and the interaction between EIF3D and RUVBL1 on cell viability, colony formation, apoptosis, and DNA damage were detected through MTT, colony formation, flow cytometry, and immunofluorescence assays, and those on in vivo tumorigenesis through murine xenograft assay. IC50 value of 5‐Fu for CRC cells was determined by probit regression analysis. Expressions of EIF3D, eIF4E, EIF3D‐associated genes, γH2AX, Bcl‐2, Bax, and Cleaved Caspase‐3/Caspase‐3 in CRC tissues, cells, and/or xenograft tumors were analyzed by qRT‐PCR and/or Western blot. Results EIF3D and RUVBL1 were highly expressed and positively correlated with CRC tissues/cells. In CRC cells, except for eIF4E, both EIF3D and RUVBL1 levels were upregulated by 5‐Fu treatment; in addition to that, RUVBL1 level was downregulated by EIF3D silencing rather than eIF4E. Meanwhile, EIF3D silencing diminished IC50 value of 5‐Fu and potentiated 5‐Fu‐induced viability decrease, colony formation inhibition, apoptosis promotion, Bcl‐2 downregulation, and γH2AX, Bax, and Cleaved Caspase‐3/Caspase‐3 upregulation but reversed 5‐Fu‐triggered RUVBL1 upregulation. RUVBL1 overexpression offsets EIF3D silencing‐induced viability decrease and apoptosis promotion of 5‐Fu‐treated CRC cells, and tumorigenesis suppression and apoptosis promotion in 5‐Fu‐treated mice. Conclusion EIF3D promotes resistance to 5‐Fu in CRC through upregulating RUVBL1 level.

Background. Colorectal cancer is highly prevalent and causes high global mortality, and glucagon axis has been implicated in colon cancer. The present study is aimed at investigating the regulating mechanisms of glucagon involvement in colorectal cancer. Methods. Publicly available data from the TCGA database was utilized to explore the expression pattern and regulating role of glucagon (GCG) in colorectal cancer (COADREAD) including colon adenocarcinomas (COAD) and rectum adenocarcinomas (READ). Statistical analyses were performed using the R software packages and public web servers. The expression pattern and prognostic significance of GCG gene in pan-cancer and TCGA-COADREAD data were investigated by performing unpaired and paired sample analyses. The association of GCG expression with clinical characteristics was investigated using logistic regression analysis. Univariate cox regression analysis was performed to test the prognostic value of GCG expression for overall survival in COADREAD patients. GCG-significantly correlated genes were obtained. Biological functions and signaling pathways were identified by performing functional enrichment analysis and Gene Set Enrichment Analysis (GSEA). Additionally, the potential involvement of GCG in tumor immunity was researched by investigating the correlation between GCG expression and 24 tumor infiltrating immune cells. Results. GCG was found to be significantly downregulated in COADREAD tumor samples compared with healthy control samples. GCG gene was shown to be associated with the prognostic outcomes of COADREAD, whereby its upregulation predicted improved survival outcomes. Functional enrichment analysis showed that the top 100 positively and top 100 negatively GCG-correlated genes were mainly enriched in three signaling pathways including ribosome, nitrogen metabolism, and proximal tubule bicarbonate reclamation. The GSEA showed that GCG-significantly correlated genes were mainly enriched in cell cycle-related pathways (reactome cell cycle, reactome cell cycle mitotic, reactome cell cycle checkpoints, reactome M phase, Reactome G2 M DNA damage checkpoint, and Reactome G2 M checkpoints), neuropeptide ligand receptor interaction, RHO GTPases signaling, WNT signaling, RUNX1 signaling, NOTCH signaling, ESR signaling, HCMV infection, and oxidative stress-related signaling. GCG was positively correlated with Th17 cells, pDC, macrophages, TFH cells, iDC, Tem, B cells, dendritic cells, neutrophils, mast cells, and eosinophils and was negatively associated with NK cells. Conclusions. GCG dysregulation with high prognostic value in COADREAD was noted. Several tumor progression-related pathways and tumor immune-modulatory cells were linked to GCG expression in COADREAD. Therefore, GCG may be regarded as a potential therapeutic target for treating colorectal cancer.