Screening of biomarkers associated with diagnosis and prognosis of colorectal cancer.

We aimed to explore biomarkers associated with diagnosis and prognosis of colorectal cancer. Differentially expressed protein (DEP) genes were obtained and validated. Moreover, co-expressed genes were screened and their prognostic value was evaluated. In addition, miRNAs that were negatively correlated with DEP genes were identified and used to construct a competitive endogenous RNA network. Furthermore, a support vector machine model was built using DEP genes, and a receiver operating characteristic curve was implemented to confirm its prediction performance. The results showed that only one DEP gene, CCL26, was obtained. Moreover, 43 genes co-expressed with CCL26 were identified, among which six (AP3M2, DAPK1, ISYNA1, PPM1K, PRR4 and RNF122) were linked with the prognosis of colorectal cancer. Besides, the axis RP11-47122.2/RP11-527N22.1-hsa-miR-3192-5p-CCL26 was identified as an lncRNA-miRNA-target gene network. Support vector machine model analysis showed that the area under the curve of CCL26 reached 0.878 based on GEO data and 0.743 based on our protein data. In conclusion, AP3M2, DAPK1, ISYNA1, PPM1K, PRR4, RNF122, CCL26 and hsa-miR-3192-5p appear to be related to the progression of colorectal cancer.

IL-8, MSPa, MIF, FGF-9, ANG-2 and AgRP collection were identified for the diagnosis of colorectal cancer based on the support vector machine model.

Colorectal cancer (CRC) is one of the most common cancer, and the early detection of CRC is essential to improve the survival rate of patients. To identify diagnostic markers for colorectal cancer (CRC) by screening differentially expressed proteins (DEPs) in CRC. The DEPs were initially obtained from 12 CRC samples and 12 healthy control samples, and verification analysis was performed in another 34 CRC samples and 34 normal controls. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment with DEPs was analyzed by the R package clusterProfiler (Version 3.2.11), and the DEP-associated protein-protein interaction (PPI) network was created from the STRING database. Additionally, Support Vector Machine (SVM) model prediction and survival analyses were conducted on the key DEPs. Preliminary screening and functional analysis showed that the DEPs mainly overrepresented in pathways such as cytokine-cytokine receptor interaction, chemokine signaling pathway, Rap1, Ras, and MAPK signaling pathways. The key DEPs, including AgRP, ANG-2, Dtk, EOT3, FGF-4, FGF-9, HCC-4, IL-16, IL-8, MIF, MSPa, TECK, TPO, TRAIL R3, and VEGF-D, were used to construct a custom chip. The drug-gene interaction network suggested that TPO was a key drug target. ROC curve showed the SVM diagnostic model with the DEPs IL-8, MSPa, MIF, FGF-9, ANG-2, and AgRP had better diagnostic performance with an AUC of 0.933. Survival analysis showed the expression of FGF9, TPO, TRAIL R3, Dtk, TECK and FGF4 were associated with prognosis. This study revealed the important serum proteins in the pathogenesis of CRC, which might serve as useful and noninvasive predictors for the diagnosis of CRC.

Identification of an MiRNA-mRNA Regulatory Network in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is the fourth most prevalent cancer in the world. However, the molecular mechanism underlying CRC is largely unknown. OBJECTIVE: To explore the pathogenic mechanism of CRC and to facilitate better diagnosis and treatment of this disease. METHODS: Differentially expressed miRNAs (DEMs) and genes (DEGs) in CRC vs. Control samples from the miRNA expression data in GSE115513 and the miRNA and mRNA expression data in the TCGA-COAD dataset were screened, followed by the construction of the miRNAmRNA regulatory network. Functional and pathway enrichment analysis, protein-protein interaction (PPI) analysis, and survival analysis were then performed for these DEGs and DEMs. RESULTS: We identified 64 DEMs from the GSE115513 dataset and 265 DEMs and 2218 DEGs from the TCGA-COAD dataset. miR-27a-3p was a hub DEM with the highest degree in the miRNA-mRNA network, while GRIN2B and PCDH10 were hub DEGs targeted by multiple miRNAs, including miR-27a-3p. SNAP25 and GRIN2B were also hub DEGs with the highest degree of interactions in the PPI network. These DEMs and DEGs were significantly enriched in multiple KEGG pathways, including proteoglycans expression and cAMP signaling pathway in cancer. Finally, seven DEGs, including FJX1 Dsc2, and hsa-miR-375, were revealed to be correlated with CRC prognosis. CONCLUSION: Aberrant expressions of genes and miRNAs were involved in the pathogenesis of CRC, probably by regulating proteoglycans expression and cAMP signaling. miR-27a-3p, PCDH10, GRIN2B, FJX1, Dsc2, and hsa-miR-375 were identified as potential targets for understanding the pathogenic mechanism of CRC. In addition, FJX1, Dsc2 and hsa-miR-375 were identified as potential predictive markers for CRC prognosis.

Correction: MicroRNA-21 promotes TGF-ß1-induced epithelial-mesenchymal transition in gastric cancer through up-regulating PTEN expression.

[This corrects the article DOI: 10.18632/oncotarget.11888.].

LncRNA-UCA1 modulates progression of colon cancer through regulating the miR-28-5p/HOXB3 axis.

Emerging evidence has shown that the long noncoding RNA urothelial carcinoma-associated 1 (UCA1) plays a tumor-promoting role in colorectal cancer, while miR-28-5p shows tumor-inhibitory activity in several tumor types. However, the mechanisms both of these in colon cancer progression are still unknown. In this work, the detailed roles and mechanisms of UCA1 and its target genes in colon cancer were studied. The results showed that UCA1 was upregulated in colon cancer tissues when compared with the adjacent nonhumorous tissues, as well as in the various colon cancer cell lines, but the expression of miR-28-5p showed an opposite trend. Furthermore, a high UCA1 level in colon cancer tissues is positively associated with the tumor size and advanced tumor stages. Functional assays revealed that both UCA1 knockdown and miR-28-5p overexpression could inhibit colon cancer cell growth and migration. Further mechanistic studies indicated that UCA1 knockdown played tumor suppressive roles in SW480 and HT116 cells through binding with miR-28-5p. We also, for the first time, identified HOXB3 as the target gene of miR-28-5p and that HOXB3 overexpression could mediate the functions of UCA1 in cell proliferation and migration of colon cancer cells. In conclusion, our data provided evidence for the regulatory network of UCA1/miR-28-5p/HOXB3 in colon cancer, suggesting that UCA1, miR-28-5p, and HOXB3 are the potential targets for colon cancer therapy.

MicroRNA-21 promotes TGF-ß1-induced epithelial-mesenchymal transition in gastric cancer through up-regulating PTEN expression.

This study aimed to explore the effects of miR-21 and PTEN/Akt signaling pathway on TGF-ß1-induced epithelial-mesenchymal transition (EMT) in gastric cancer (GC). GC tissues and adjacent tissues were collected from 83 patients. The qRT-PCR assay was performed to detect miR-21 expression. The expressions of PTEN, Akt and p-Akt were detected by immunohistochemistry. After 48 h of treatment with TGF-ß1 (10 ng/mL), the SGC-7901 and KATO-III cells were divided into the blank, negative control (NC), miR-21 inhibitors, PTEN-siRNA and miR-21 inhibitors + PTEN-siRNA groups. EMT related factors and PTEN expressions were detected by qRT-PCR assay and Western blotting. The scratch test was conducted to observe cell migration. Xenograft tumor model in nude mice was used to evaluate the effects of miR-21 on EMT of GC cells in vivo. In GC tissues, the expressions of miR-21, Akt and p-Akt were up-regulated, while PTEN expression was down-regulated. Gene and protein expressions of E-cadherin and PTEN in the miR-21 inhibitors group were higher than the blank, NC, PTEN-siRNA and miR-21 inhibitors + PTEN-siRNA groups, while the expressions of N-cadherin, ß-catenin, Vimentin and Slug in the miR-21 inhibitors group were lower than other groups. MiR-21 inhibitors significantly inhibit cell migration and invasion in GC cell lines. In vivo xenograft experiment revealed that miR-21 inhibitor inhibits the growth of transplanted tumor through up-regulating E-cadherin and PTEN expressions and down-regulating the expressions of N-cadherin, ß-catenin, Vimentin and Slug. These results suggest that miR-21 could promote TGF-ß1-induced EMT in GC cells through up-regulating PTEN expression.

Hydroxyflavanone inhibits gastric carcinoma MGC-803 cell proliferation.

Gastric carcinoma (GC) is the most common primary malignancy of the digestive tract, with increasing incidence in many countries. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess inhibition of HepG2 cell proliferation by 2'-hydroxyflavanone. The STAT3 pathway was performed. 2'-hydroxyflavanone reduced inhibitory effects on MGC-803 cell proliferation. 2'-hydroxyflavanone exhibited the highest inhibition rate. Treatment of MGC-803 cells with 400, 200, and 100 µg/ml 2'-hydroxyflavanone resulted in 88.9±0.7%, 81.2±0.5%, 68.4±0.5% decrease in cell viability, respectively, indicating an IC50 of 9.3 µg/ml. The 100 µg/ml 2'-hydroxyflavanone can significantly inhibit the STAT3 pathway activation. 2'-hydroxyflavanone inhibits MGC-803 cell proliferation by inhibiting STAT3 pathway activation. This extract is therefore a potential drug candidate for treatment of liver cancer.