Aberrant miR-199a-3p expression has been reported in several cancers. However, the clinical significance of miR-199a-3p in human colorectal cancer has not been addressed. In this study, we detected miR-199a-3p expression in 92 colorectal cancer cases to evaluate its clinicopathologic characteristics in colorectal cancer. We showed that miR-199a-3p expression was significantly upregulated in cancer tissues than NATs. Clinicopathologic analysis revealed that high miR-199a-3p expression contributed to more advanced lymphatic invasion, lymph node metastasis, liver metastases and late TNM stage in colorectal cancer. Kaplan-Meier analysis showed that high expression of miR-199a-3p could lead to a significantly shorter overall survival rate. Cox's proportional hazards model also indicated that the high expression of miR-199a-3p could serve as an independent and significant prognostic factor for survival. We transfected miR-199a-3p inhibitor into SW480 cells and observed that miR-199a-3p inhibitor could markedly inhibit the cell proliferation. Flow cytometry analysis also found that miR-199a-3p inhibitor could cause G0/G1 arrest, decreased percentage of S and G2/M phase and induce more cell apoptosis in SW480 cells. These results suggested that miR-199a-3p may serve as an efficient biomarker for diagnosis and novel prognostic indicator in colorectal cancer.

Circulating microRNAs are novel and non-invasive tumor biomarkers for colorectal cancer (CRC) detection. In this study, we investigated miR-372 expression in serum and tissues in CRC and colorectal precancerous lesions (CPL) patients by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Our data demonstrated that serum or tissue miR-372 levels were significantly up-regulated in patients with CRC or CPL, compared to healthy control (HC) subjects or normal tissues (P<0.05). High miR-372 expression in early colorectal cancer (ECRC) tissues were statistically significantly associated with tumor size (P<0.05), Tumor-Nodes-Metastasis (TNM) stage (P<0.05), and led to a worse overall survival (P=0.012). Postoperative serum miR-372 levels in ECRC patients significantly dropped, compared to the corresponding preoperative levels (P<0.05). The AUC of serum miR-372 expression for ECRC diagnosis was 0.854, which was significantly higher than that of combined tumor markers (CEA, CA19-9 and CA12-5) (0.613) (P<0.05). The sensitivity and specificity of serum miR-372 expression for ECRC diagnosis were 81.9 % and 73.3 %. All these findings provided an evidence that serum miR-372 could be a noninvasive biomarker for the early detection and prognosis of CRC.

Patients with ulcerative colitis (UC) are at increased risk of developing colitis‑associated colon cancer. Previous studies have indicated that interleukin (IL)‑21, which is predominantly secreted by follicular T helper (Tfh) cells, is overproduced in inflammatory bowel diseases. In order to investigate the role of IL‑21 in UC and the association between IL‑21 and Tfh cells, the number of Tfh cells and the level of IL‑21 were investigated in colonic tissues from UC patients and wild‑type (WT) mice, which were induced by dextran sulphate sodium (DSS). High Tfh cell counts and levels of IL‑21 were observed in UC patients and WT mice with DSS‑induced colitis. Subsequent comparison of the mucosal damage and expression of Tfh‑associated cytokines in the WT mice and IL‑21 knockout (IL‑21KO) mice following DSS administration, revealed that IL‑21KO mice were largely protected against colitis and exhibited reduced infiltration of Tfh cells, as well as decreased production of Tfh‑associated cytokines. The present study also found that IL‑21 was necessary for the proliferation and secretion of Tfh cells in vitro. In addition, neutralization of IL‑21 in DSS‑administered WT mice using anti‑IL‑21 reduced the number of Tfh cells and the level of mucosal damage. Administration of a neutralizing IL‑21 antibody decreased the colonic infiltration of Tfh cells and reduced damage to the mucosa. These results indicated that Tfh cells are important in UC and that its effector molecule, IL‑21, is not only a critical regulator of inflammation, but also regulates the proliferation and response of Tfh cells in the colitis microenvironment.

BackgroundThe Forkhead box M1 (FOXM1) is an oncogenic transcription factor and plays a significant role in cell EMT, proliferation, metastasis in a multitude of human solid tumors including colorectal cancer (CRC). However, the underlying molecular mechanisms by which FoxM1 contributes to epithelial-to-mesenchymal (EMT) and metastasis have not been fully elucidated in CRC.MethodsIn our study, we investigated FOXM1 protein expression in 87 CRC tissue specimens, invasive lymph nodes and adjacent paired normal colorectal tissues by immunohistochemical analysis. Then we transfected FOXM1 specific shRNA into SW620 cells to examine effect of FOXM1 on proliferation, colony formation, migration and invasion in vitro. Western blotting and real-time PCR were used to detect the protein and mRNA expression of FOXM1 and EMT-related markers.ResultsFOXM1 was overexpressed in CRC tissues, invasive lymph nodes and CRC cell lines. FoxM1 overexpression was significantly associated with lymph node metastasis (P < 0.001), and tumor recurrence (P < 0.001). Moreover, downregulation of FOXM1 in SW620 cells by shRNA approach inhibited cell growth, clonogenicity, migration and invasion in vitro. In addition, decreased FOXM1 expression in SW620 cells reversed the acquisition of EMT phenotype by up-regulating E-cadherin, as well as reduction Vimentin and Snail expressions at protein and mRNA levels.ConclusionsFOXM1 may regulate CRC cells metastasis through EMT program and FOXM1 may be a potential target for treatment of CRC.

Rho GDP dissociation inhibitor 2 (RhoGDI2) has been identified as a regulator of tumor metastasis, although its role in tumor progression remains controversial. In this study, we examined the expression of RhoGDI2 in PC tissues and cell lines. To investigate the function of RhoGDI2 in PC cells, RhoGDI2 expression was depleted in PANC-1 and Patu8988 cells by small interfering RNA (siRNA). RhoGDI2 was found to be overexpressed in pancreatic carcinoma (PC) tissues and PC cell lines. Additionally, the results showed that depletion of RhoGDI2 significantly inhibited cell motility and invasion in vitro, but did not affect cell proliferation. The clinical study together with the experimental data confirmed that RhoGDI2 modulated the expression of matrix metalloproteinase 2 (MMP2). Taken together, findings of the present study indicated that RhoGDI2 is involved in pancreatic tumor malignancy and metastasis. Thus, RhoGDI2 is a potential target for the gene therapy of PC.

Abstract. Aberrant expression of pancreatic adenocarcinoma upregulated factor (PAUF), a novel secretory protein, has been reported in several types of cancer. However, in colorectal cancer (CRC), whether PAUF also plays its oncogenic role through the Wnt/β-catenin pathway and its effect in regulating malignant phenotypes of CRC is unknown. In this study, we detected PAUF and β-catenin expression levels by immunohistochemical analysis and real-time PCR in CRC tissues, adjacent non-tumor tissues (NATs) and 5 CRC cell lines. The results demonstrated that the expression of PAUF and β-catenin in tumor tissues was higher than in NATs. Moreover, the expression of PAUF was correlated with the expression of β-catenin in both tumor tissues and NATs. The HCT116 cell line, which has the highest PAUF expression of the 5 cell lines, was transfected with small interfering RNA (siRNA) targeting on PAUF, which significantly downregulated the expression of PAUF in cancer cells. Successful transfection was confirmed by using RT-PCR and western blot analysis. Further studies demonstrated that PAUF-siRNA inhibited the proliferation of CRC cells, promoted their apoptosis and induced G0/G1 cell cycle arrest. At the same time, PAUF-siRNA inhibited the invasion, adhesion and migration of the tumor cells. In conclusion, this study suggested that PAUF was expressed in CRC at a high frequency. Interference of PAUF may be an effective strategy for regulating malignant phenotypes of CRC through the Wnt/β-catenin pathway.

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Gastric cancer (GC) is among the most prevalent causes of cancer-related death globally. MiR-223 has been implicated in a variety of cellular mechanisms linked to cancer progression. However, the miR-223 expressions and its function in GC are unknown. We discovered that miR-223 expression was raised in GC tissues in comparison with nearby normal tissues in this investigation. Additionally, multiplied miR-223 expression was strongly linked with TNM stage ( p = 0.022 ), live metastasis ( p = 0.004 ),lymph node metastasis ( p = 0.004 ),and Borrmann type and was associated with an unfavorable prognostic for patients with GC. Furthermore, suppressing miR-223 significantly increased cell death and prevented cell migration and invasion in vitro. Additionally, miR-223 silencing decreased tumor development in vivo. Additionally, we discovered that miR-223 enhanced GC development by specifically targeting RhoB. In summary, our findings reveal that miR-223 increases tumor progression in GC by targeting RhoB, suggesting that it could serve to be a potential biomarker for the prediction of the disease.