Background/Aim: Lung cancer is the second most common cancer in both men and women, after prostate and breast cancer, respectively. There are two main types of primary lung cancer, non-small cell lung cancer (NSCLC), which accounts for approximately 85-90% of all lung cancer cases, and small cell lung cancer (SCLC), which accounts for the other 10-15% of lung cancers. MiRNAs are small molecules that post-transcriptionally regulate many genes and contribute to many disease aetiologies, including tumours. In lung cancer, the down-regulation of miR-140-5p leads to disease progression. Materials and Methods: In this study a miR-140-5p-only treatment and miR-140-5p combined with other chemotherapeutics have been studied in vitro. Results: When transfected into NSCLC, the overexpression of miR-140-5p reduced the migration and invasion properties of malignant cells and, also improved their adhesion onto the artificial extracellular matrix. When miRNA-140-5p replacement treatment was combined with other drugs commonly used in clinical practice, such as gefinitib, DMH1 and cisplatin, it enhanced their efficacy by reducing the migration and invasion ability of cancer cells, thus suggesting that it acts synergistically with known compounds for the treatment of NSCLC. Additionally, some endothelial mesenchymal transition (EMT) markers appeared to be regulated by miR-140-5p. Conclusion: Novel direct targets of miR-140-5p have not been investigated in this study, but our results indicate the involvement of miR-140-5p in lung cancer invasion. The preliminary data from this study imply that when miR-140-5p levels are restored; maybe synergistically support current therapies for NSCLC though further validation, especially in vivo is required.

Background: S100A11 is a member of the S100 family of proteins containing two EF-hand calcium-binding motifs. The dysregulated expression of the S100A11 gene has been implicated in tumour metastasis. However, the role of S100A11 protein in tumour cell response to chemotherapeutic drugs has not been characterised.Methods: Transcript levels of S100A11 in gastric cancer were evaluated using an in-house patient cohort. Protein expression of S100A11 in gastric cancer was estimated by immunohistochemistry of a tissue microarray. The stable gastric cancer cell lines were established using lentiviral shRNA vectors. The knockdown of S100A11 was validated by qRT-PCR, PCR, and Western blot. The cellular function of S100A11 was estimated by assays of cell adhesion, migration, and invasion. The cell cytotoxic assay was performed to investigate the response to chemotherapeutic drugs. An unsupervised hierarchical clustering and principal component analysis (HCPC) was applied to unveil the dimensional role of S100A11 among all S100 family members in gastric cancer.Results: High expression of S100A11 is associated with poor survival of gastric cancer patients (p < 0.001, HR = 1.85) and is an independent prognostic factor of gastric cancer. We demonstrate that S100A11 plays its role as a tumour promoter through regulating the MMP activity and the epithelial-mesenchymal transition (EMT) process. The stable knockdown of S100A11 suppresses the metastatic properties of gastric cancer cells, which include enhancing cell adhesion, but decelerating cell migration and invasion. Furthermore, the knockdown of S100A11 gene expression dramatically induces the cellular response of gastric cancer cells to the first-line chemotherapeutic drugs fluoropyrimidine 5-fluorouracil (5-FU) and cisplatin.Conclusion: The present study identifies S100A11 as a tumour promoter in gastric cancer. More importantly, the S100A11-specific targeting potentially presents dual therapeutic benefits by not only controlling tumour progression but also sensitising chemotherapeutic cytotoxic response.

Background/Aim: Colorectal cancer (CRC) is the third most common cancer in the world. The high mortality of this tumor is mainly due to its invasive properties, as it forms metastases in multiple organs, preferentially in the liver. There has evidence showing that C-X-C chemokine receptor type 4 (CXCR-4) and its ligand, stromal cell-derived factor-1 (SDF-1), plays an important role in cancer progression and metastasis. However, the molecular mechanism underling the CRCR4-mediated CRC metastasis has not been well characterized. In this study, we aimed to investigate the roles of CXCR4 in colorectal cancer using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-based genomic editing technique. Materials and Methods: We knocked-down CXCR4 using specific guide-RNA linked CRISPR/Cas9 in HT115 and COLO201 colon cancer cell lines which exhibited high levels of endogenous CXCR4 gene expression. Stable HT115 cells with CXCR4 knock-down were established by CRISPR plasmid transfection and validation was confirmed using T7 endonuclease 1 (T7EN1), flow cytometry (FACS) and western blotting assays. Results: Knock-down of CXCR4 did not decrease proliferation of HT115 cells, but decreased the adhesion potential of cells to the human umbilical vein endothelial cells (HUVEC) and extracellular matrix. We further demonstrated that the AKT and type 1 insulin-like growth factor receptor (IGF1R) signalling pathways may be involved in the alteration of adhesion in CRC cells when CXCR4 is knocked down. Conclusion: Our data suggest that CXCR4 plays a key role in colorectal cancer progression via the mediation of tumor cell adhesion.

DEAD/H box helicases are implicated in lung cancer but have not been systematically investigated for their clinical significance and function. In this study, we aimed to evaluate the potential of DEAD/H box helicases as prognostic biomarkers and therapeutic targets in lung cancer by integrated bioinformatic analysis of multivariate large-scale databases. Survival and differential expression analysis of these helicases enabled us to identify four biomarkers with the most significant alterations. These were found to be the negative prognostic factors DDX11, DDX55 and DDX56, and positive prognostic factor DDX5. Pathway enrichment analysis indicates that MYC signalling is negatively associated with expression levels of the DDX5 gene while positively associated with that of DDX11, DDX55 and DDX56. High expression levels of the DDX5 gene is associated with low mutation levels of TP53 and MUC16, the two most frequently mutated genes in lung cancer. In contrast, high expression levels of DDX11, DDX55 and DDX56 genes are associated with high levels of TP53 and MUC16 mutation. The tumour-infiltrated CD8 + T and B cells positively correlate with levels of DDX5 gene expression, while negatively correlate with that of the other three DEAD box helicases, respectively. Moreover, the DDX5-associated miRNA profile is distinguished from the miRNA profiles of DDX11, DDX55 and DDX56, although each DDX has a different miRNA signature. The identification of these four DDX helicases as biomarkers will be valuable for prognostic prediction and targeted therapeutic development in lung cancer.