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Background: Metastasis of colorectal cancer (CRC) extremely affects the prognosis of CRC patients. Recently, the genetic methylation has been shown to associate with tumor metastasis. This research aimed to explore the Syk gene, which is frequently hypermethylated in different cancers, and its impact on the metastasis of CRC cells. Methods: We employed the UALCAN database for the detection of the methylation levels of Syk in different cancers. CIBERSORT, TIMER and TISIDB tools were employed to analyze the association of Syk expression with immune features of CRC. Treatment with decitabine has been noted to restore the expression of Syk in CRC cells. The invasion and migration abilities of CRC cell lines were determined using transwell and wound healing assays. The correlation between Syk and c‐Myc was established using the GEPIA2 database and Western blot assays. ​Results: Our results, based on UALCAN, revealed that the methylation level of Syk was altered in diverse cancers including colon adenocarcinoma. We found that expression profile and methylation level of Syk was correlated with immune features of colon adenocarcinoma. Decitabine can restore the expression of Syk in HCT116 and SW480 cells, hence affecting their migration and invasion. Results from GEPIA2 showed that Syk expression was correlated with c‐Myc, while Western blotting analysis revealed a negative association between the expression level of Syk and c‐Myc. ​Conclusions:​ ​This study demonstrates that the expression of Syk could be restored by decitabine in colorectal cancer, thus affecting the migration and invasion abilities of CRC cells. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have been characterized by playing a crucial role in tumorigenesis. However, the detail biological function and clinical importance of lncRNAs in colorectal cancer (CRC) are unclear and have attracted different levels of in-depth research. In this context, we explored the differentially expressed profiles of lncRNAs in six CRC tissues and three adjacent non-tumor tissues from RNA-sequencing (RNA-seq) study and noted a lncRNA, RP11-51O6.1, which is markedly overexpressed in CRC tissues, particularly in aggressive cases. Impressively, an elevated RP11-51O6.1 level was highly correlated with poor prognosis in clinical patients. Functional analyses revealed that RP11-51O6.1 could promote cell proliferation in vitro and in vivo. Furthermore, we reported that RP11-51O6.1 enhances cell migration and invasion in vitro. Mechanistic studies (Bioinformatics binding site analyses, the Luciferase reporter, Ago2 immunoprecipitation, the RNA pull-down, immunofluorescence colocalization, rescued assays and western blotting) implicated that RP11-51O6.1 could regulate YAP1 expression by competitively sponging miR-206 and blocking its activity in promoting CRC progression. Conclusively, our findings identify a novel RP11-51O6.1/miR-206/YAP1 regulatory axis that participates in CRC progression and development, suggesting RP11-51O6.1 is an exploitable biomarker and appealing therapeutic target in treating CRC. [ABSTRACT FROM AUTHOR]

Background: Preoperative accurate prediction of lymph node status is especially important for the formulation of treatment plans for patients with gastric cancer (GC). The purpose of this study was to establish decision rules and a risk assessment model for lymph node metastasis (LNM) in GC using preoperative indicators. Methods: The clinical data of 554 patients who underwent gastrectomy with D2 lymphadenectomy were collected. A 1:1 propensity score matching (PSM) system was used, and the clinical data of the matched 466 patients were further analyzed. The important risk factors for LNM were extracted by the random forest algorithm, and decision rules and nomogram models for LNM were constructed with a classification tree and the "rms" package of R software, respectively. Results: Tumor size (OR : 2.058; P = 0.000), computed tomography (CT) findings (OR : 1.969; P = 0.001), grade (OR : 0.479; P = 0.000), hemoglobin (Hb) (OR : 1.211; P = 0.005), CEA (OR : 1.111; P = 0.017), and CA19-9 (OR : 1.040; P = 0.033) were independent risk factors for LNM in GC. Tumor size did rank first in the ranking of important factors for LNM in GC and was the first-level segmentation of the two initial branches of the classification tree. The accuracy, sensitivity, specificity, and positive predictive value of the decision rules in diagnosing preoperative LNM in GC were 75.6, 85.7, 73.9, 73.5, and 79.3%, respectively. The accuracy, sensitivity, and specificity of the risk assessment model in predicting preoperative LNM in GC were 79.3, 80.3, and 79.4%, respectively. Conclusion: Tumor size was the most important factor for evaluating LNM in GC. This decision rules and nomogram model constructed to take into account tumor size, CT findings, grade, hemoglobin, CEA, and CA19-9 effectively predicted the incidence of LNM in preoperative GC. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) acting as crucial regulators in tumorigenesis. However, its biological functions of lncRNAs in colorectal cancer (CRC) have not been systematically clarified. Methods: An unbiased screening was performed to identify disregulated lncRNAs revealed to be implicated in CRC carcinogenesis according to an online-available data dataset. In situ hybridization (ISH), RT-qPCR and RNA fluorescence in situ hybridization (RNA-FISH) were applied to detect RP11-757G1.5 expression in CRC tissues and cell lines. The associations of RP11-757G1.5 with clinicopathological characteristics were analyzed. Their effects on prognosis were analyzed by the Kaplan-Meier analysis, Log-rank test, Univariate and Multivariate Cox regression analysis. The potential biological function of RP11-757G1.5 in CRC was investigated by Colony formation, Edu cell proliferation, Flow cytometry, Wound healing and Transwell assays. Bioinformatics binding site analysis, Luciferase reporter assay, Ago2 immunoprecipitation assays, RNA pull-down assay, RT-qPCR and Western blotting were utilized to demonstrate the mechanism of RP11-757G1.5 acts as a molecular sponge of miR-139-5p to regulate the expression of YAP1. Finally, we further explore the potential role of RP11-757G1.5 in CRC orthotopic xenografts in vivo. Results: We discovered a novel oncogenic lncRNA RP11-757G1.5, that was overexpressed in CRC tissues, especially in aggressive cases. Moreover, up-regulation of RP11-757G1.5 strongly correlated with poor clinical outcomes of patients with CRC. Functional analyses revealed that RP11-757G1.5 promoted cell proliferation in vitro and in vivo. Furthermore, RP11-757G1.5 stimulated cell migration and invasion in vitro and in vivo. Mechanistic studies illustrated that RP11-757G1.5 regulated the expression of YAP1 through sponging miR-139-5p and inhibiting its activity thereby promoting CRC progression and development. Conclusions: Altogether, these results reveal a novel RP11-757G1.5/miR-139-5p/YAP1 regulatory axis that participates in CRC carcinogenesis and progression. [ABSTRACT FROM AUTHOR]

Background: MYO18B has been identified as a novel tumor suppressor gene in several cancers. However, its specific roles in the progression of hepatocellular carcinoma (HCC) has not been well defined. Methods: We firstly identified the expression and prognostic values of MYO18B in HCC using TCGA cohort and our clinical data. Then, MYO18B knockdown by RNA inference was implemented to investigate the effects of MYO18B on HCC cells. Quantitative RT-PCR and Western blot were used to determine gene and protein expression levels. CCK-8 and colony formation assays were performed to examine cell proliferation capacity. Wound healing and transwell assays were used to evaluate the migration and invasion of HepG2 cells. Results: MYO18B was overexpressed and correlated with poor prognosis in HCC. MYO18B expression was an independent risk factor for overall survival. Knockdown of MYO18B significantly inhibited the proliferation, migration and invasion of HepG2 cells. Meanwhile, MYO18B knockdown could effectively suppress the phosphorylation of PI3K, AKT, mTOR and P70S6K, suggesting that MYO18B might promote HCC progression by targeting PI3K/AKT/mTOR signaling pathway. Conclusions: MYO18B promoted tumor growth and migration via the activation of PI3K/AKT/mTOR signaling pathway. MYO18B might be a promising target for clinical intervention of HCC. [ABSTRACT FROM AUTHOR]