A bioinformatics framework to identify the biomarkers and potential drugs for the treatment of colorectal cancer.

Colorectal cancer (CRC), a common malignant tumor, is one of the main causes of death in cancer patients in the world. Therefore, it is critical to understand the molecular mechanism of CRC and identify its diagnostic and prognostic biomarkers. The purpose of this study is to reveal the genes involved in the development of CRC and to predict drug candidates that may help treat CRC through bioinformatics analyses. Two independent CRC gene expression datasets including The Cancer Genome Atlas (TCGA) database and GSE104836 were used in this study. Differentially expressed genes (DEGs) were analyzed separately on the two datasets, and intersected for further analyses. 249 drug candidates for CRC were identified according to the intersected DEGs and the Crowd Extracted Expression of Differential Signatures (CREEDS) database. In addition, hub genes were analyzed using Cytoscape according to the DEGs, and survival analysis results showed that one of the hub genes, TIMP1 was related to the prognosis of CRC patients. Thus, we further focused on drugs that could reverse the expression level of TIMP1. Eight potential drugs with documentary evidence and two new drugs that could reverse the expression of TIMP1 were found among the 249 drugs. In conclusion, we successfully identified potential biomarkers for CRC and achieved drug repurposing using bioinformatics methods. Further exploration is needed to understand the molecular mechanisms of these identified genes and drugs/small molecules in the occurrence, development and treatment of CRC.

MiR-483 Promotes Colorectal Cancer Cell Biological Progression by Directly Targeting NDRG2 through Regulation of the PI3K/AKT Signaling Pathway and Epithelial-to-Mesenchymal Transition.

BACKGROUND: Colorectal cancer is the third frequent tumor in the whole world. MiR-483, located at the 11p15.5 locus, acts as an oncogene in multiple tumors. The purpose of this study is to explore the important roles of miR-483 in colorectal cancer. MATERIALS AND METHODS: RT-qPCR and western blot were applied to calculate the mRNA levels of miR-483 and genes. The Kaplan-Meier method was conducted to calculate the survival of patients with colorectal cancer. The proliferation and invasive abilities were measured by Methyl Thiazolyl Tetrazolium (MTT) and transwell assays. RESULTS: MiR-483 was upregulated in colorectal cancer tissues, and the upregulation of miR-483 predicted poor prognosis of colorectal cancer patients. NDRG2 was a target gene of miR-483 in colorectal cancer. Furthermore, miR-483 has been reported to promote colorectal cancer cell proliferation and invasion through targeting NDRG2 by the PI3K/AKT pathway and epithelial-to-mesenchymal transition (EMT). In addition, the overexpression of miR-483 promoted xenograft growth of LOVO cells. CONCLUSION: MiR-483 promoted cell proliferation through the NDRG2/PI3K/AKT pathway and invasion-mediated EMT in colorectal cancer. In view of the multiple mechanisms of molecular immunotherapy, it is necessary to further study the relationship between miR-483 and colorectal cancer, so as to find a more direct and effective treatment method to prevent colorectal cancer.

LINC00511 promotes gastric cancer cell growth by acting as a ceRNA.

BACKGROUND: Gastric cancer (GC) is one of the most aggressive malignancies, with a high incidence and poor prognosis worldwide. Recently, accumulating evidence has illustrated that long noncoding RNAs (lncRNAs) play pivotal roles in many cancers. It has been reported that LINC00511 contributes to tumorigenesis in various diseases. However, the role of LINC00511 in GC cell growth remains mostly unknown. AIM: To determine whether the lncRNA LINC00511 exerted its carcinogenic function in GC via the miR-124-3p/PDK4 axis. METHODS: Cell culture and transfection, RNA extraction and quantitative real-time PCR, CCK-8 assay, Colony formation assay, Luciferase reporter assay, RIP assay, RNA pull-down assay, and Western blot analysis were used to show expression and mechanisms of LINC00511 in GC progression and apoptosis. Rescue assays were performed to verify the relationships among LINC00511, miR-124-3p and PDK4 further. RESULTS: The expression of LINC00511 was remarkably upregulated in GC cells compared to that in corresponding normal cell lines. Compared to the controls, cell proliferation was inhibited, and cell apoptosis was increased upon LINC00511 knockdown, demonstrating that LINC00511 influenced GC cell growth. An exploration of the molecular mechanism revealed that LINC00511 functioned as a molecular sponge of miR-124-3p and that PDK4 was a downstream target of miR-124-3p in GC. Rescue assays showed that the overexpression of PDK4 could partly restore the inhibitory function of si-LINC00511 in GC. CONCLUSION: These data demonstrate that LINC00511 promotes gastric cancer cell growth by acting as a ceRNA to regulate the miR-124-3p/PDK4 axis, which may be a promising therapeutic target for GC.

Long noncoding RNA SNHG6 functions as a competing endogenous RNA by sponging miR-181a-5p to regulate E2F5 expression in colorectal cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) have been identified as a novel class of regulators implicated in diverse biological processes in human cancers. Currently, evidence have shown that SNHG6, a cancer-associated lncRNA, exerts critical functions in gastric cancer and hepatocellular carcinoma; however, its role in colorectal cancer (CRC) remains unclear. METHODS: The expression of SNHG6 was determined by quantitative real-time PCR in CRC tissues and cells. SNHG6 was downregulated by using RNAi technology. Cell proliferation was examined by MTT and clone formation assays. Cell migration and invasion were determined by wound healing and transwell assays. Fluorescence in situ hybridization assays were performed to examine subcellular localization of SNHG6 in CRC cells. Fluorescence reporter and Western blot assays were used to explore the potential mechanisms of SNHG6 in CRC progression. RESULTS: In this study, we found that SNHG6 was significantly upregulated in CRC tissues and cell lines, compared with normal tissues and normal colorectal epithelial cell line NCM460, respectively. High expression of SNHG6 was positively correlated with tumor size, advanced TNM stage, and distant metastasis. Survival analyses revealed that SHNG6 was significantly associated with poor clinical outcomes and could serve as an independent prognostic factor. Loss-of-function studies demonstrated that SNHG6 knockdown inhibited CRC cell proliferation, induced G0/G1 arrest, promoted apoptosis, suppressed CRC cell migration and invasion, and restrained tumor growth. Mechanistic investigations showed that SNHG6 acted as a competing endogenous RNA for miR-181a-5p and attenuated the inhibitory effect of miR-181a-5p on E2F5. CONCLUSION: Taken together, these results demonstrated that SNHG6 plays a crucial role in CRC progression via miR-181a-5p/E2F5 axis. Therefore, SNHG6 may serve as a prognostic and therapeutic biomarker in CRC.

[Comparison of effects of hand-assisted laparoscopic and traditional laparoscopic right hemicolectomy on immune function].

OBJECTIVE: To compare the effects of hand-assisted laparoscopic and traditional laparoscopic right hemicolectomy on immune function. METHODS: From May 2010 to November 2013, 60 patients with right colon carcinoma were prospectively enrolled and randomly divided into hand-assisted laparoscopic surgery(HALS) group and traditional laparoscopic surgery(TLS) group with 30 cases in each group. CRP, IL-6, CD3+, CD4+, CD8+ in the peripheral blood were measured and compared on the first day before operation, the first, third and fifth day after operation. RESULTS: CRP and IL-6 levels in two groups were significantly increased on the first, third and fifth days(P<0.01), and peaked on the third day after operation. Postoperative CRP and IL-6 levels were slightly higher in HALS group, but the difference was not statistically significant (P>0.05). CD3+ and CD4+ levels were significantly decreased on the first, third day after operation(P<0.05), and returned to preoperative levels on the fifth day after operation in both two groups, and the difference was not statistically significant(P>0.05). There was no significant difference in CD8+ between two groups either before surgery or after operation(P>0.05). CONCLUSION: Hand-assisted laparoscopic right hemicolectomy has the same effects of traditional laparoscopic right hemicolectomy in the relief of postoperative stress and the protection of immune function.