Dawei Yuan

Plasma miR-183 predicts recurrence and prognosis in patients with colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. The prognosis for this cancer is poor, and the development of novel biomarkers, particularly non-invasive surrogate biomarkers, is urgently needed. Recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in the blood and can serve as useful biomarkers for various types of cancer. In this study, the miR-183 expression levels were found to be significantly overexpressed in plasma samples from CRC patients compared with controls, and the postoperative plasma miR-183 levels were significantly reduced compared with the preoperative levels. The value of the area under the receiver operating characteristic (ROC) curve obtained for miR-183 was 0.829, which was higher than those for carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). High plasma miR-183 expression was significantly associated with lymph node metastasis, distant metastasis, higher pTNM stage (III-IV), and tumor recurrence. CRC patients with elevated miR-183 expression in plasma displayed shorter disease-free survival (DFS) and lower overall survival (OS). More importantly, plasma miR-183 was independently correlated with tumor recurrence and a lower OS. Collectively, our results suggested that the elevated miR-183 in the plasma could be a promising biomarker for predicting the risk of tumor recurrence and poor survival in CRC patients.

The preoperative neutrophil–lymphocyte ratio predicts recurrence and survival among patients undergoing R0 resections of adenocarcinomas of the esophagogastric junction

Elevated preoperative neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) predict survival rates among patients with several types of cancer. The current study sought to clarify whether NLR and PLR are clinically useful independent prognostic indicators of adenocarcinomas of the esophagogastric junction (AEG) among patients undergoing curative resections (i.e., R0 resections).

MiRNA-429 suppresses the growth of gastric cancer cells in vitro

Micro-RNAs (miRNAs) have been found to be implicated in a very wide range of physiological processes. This study was aimed to investigate the regulation of miRNA-429 (miR-429) in gastric cancer cells on cell proliferation and apoptosis. Quantitative PCR was employed to detect the expressions of miR-429 after eukaryotic expression plasmid of miR-429 and its inhibitor were transiently transfected into poorly differentiated human gastric cancer cell line BGC823. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assays were used to examine proliferation ability. Apoptosis was analyzed by flow cytometry after transfection. The results showed that 48 h after transfection, overexpression of miR-429 reached maximum efficiency. Compared with mock transfection, miR-429 inhibited tumor cell proliferation significantly (P < 0.05) at 48 h and 72 h. of Overexpression of miR-429 promoted tumor cell apoptosis when compared with mock transfected cells (P < 0.05). On the contrary, miR-429 inhibitor promoted tumor cell proliferation and inhibited apoptosis when compared with controls (P < 0.05). Our results suggested that miRNA-429 may serve as a tumor suppressor during tumorigenesis of gastric cancer and may be a potential gastric cancer therapeutic target.

Elevated KIAA0101 expression is a marker of recurrence in human gastric cancer

Gastric cancer (GC) is one of the most common malignant tumors with a high rate of recurrence, which results in surgery being unsuccessful. Therefore, it is important to find the reason for the surgery failing. The purpose of the present study was to investigate a factor related to recurrence. Expression of KIAA0101 was assessed in 61 paired human primary GC and non‐cancerous gastric tissue using immunohistochemistry. After surgery, all 61 patients were followed regularly for more than 24 months or until death to analyze the 2‐year survival rate and recurrence. After suppressing KIAA0101 by RNA interference in human GC cell lines, the cell viability was detected using MTT. We are first to find that KIAA0101 was elevated in GC tissues compared with paired non‐cancerous gastric tissues. Immunohistochemical staining also revealed the predominant nuclear localization of KIAA0101 protein. Despite these findings, GC patients with elevated KIAA0101 expression levels exhibited a high recurrence and subsequently poor prognosis in the survival study. Also, cell viability was significantly inhibited after suppressing KIAA0101 in GC cells, suggesting that KIAA0101 might promote cancer cell proliferation. KIAA0101 is increased in human GC and is a marker of recurrence.

Expression of KIAA0101 protein is associated with poor survival of esophageal cancer patients and resistance to cisplatin treatment in vitro

The KIAA0101 protein is overexpressed in various human cancers, including esophageal cancer (EC). This study assessed the association of KIAA0101 protein with prognosis and resistance to chemotherapy in EC patients and then explored the role of KIAA0101 in EC cells in vitro. A total of 228 EC patients participated in the study. Tissue samples were collected for immunohistochemical analysis of KIAA0101 expression in tumor and normal tissues for association with clinicopathological and survival data. KIAA0101 cDNA or shRNA were transfected into EC cells for assessment of tumor cell viability, sensitivity to cisplatin treatment, and gene expression. Array-based comparative genomic hybridization (aCGH) was used to detect the changed copy-number alterations in cell lines expressing different levels of KIAA0101. Expression of KIAA0101 protein was upregulated in EC tissues, which was associated with pTNM stage, resistance to chemotherapy, tumor recurrence, and poor survival of EC patients. In vitro experiments showed that expression of KIAA0101 enhanced cell proliferation and upregulated cyclins A and B expression, leading to a reduced G1 phase of the cell cycle. KIAA0101 also induced resistance of EC Eca-109 and TE-1 cell lines to cisplatin treatment through a decrease in apoptosis. The aCGH data showed that levels of KIAA0101 expression altered chromosome stability, affecting genes that are associated with cancer progression. In conclusion, upregulated KIAA0101 expression is associated with EC progression, resistance to chemotherapy, and poor survival of the patients.

Paf15 expression correlates with rectal cancer prognosis, cell proliferation and radiation response.

Paf15, which participates in DNA repair, is overexpressed in numerous solid tumors. Blocking of Paf15 inhibits the growth of many types of cancer cells; while simultaneously enhancing cellular sensitivity to UV radiation. However, its expression and function in rectal cancer (RC) remain unknown. The current study was undertaken to assess the association of Paf15 expression with RC prognosis, as well as to explore the participation of Paf15 in the response of RC cells to irradiation. Increased Paf15 expression was observed in RC tissues and associated with pTNM stage and poor survival. In vitro, Paf15 induced increased RC cell proliferation while accelerating cell cycle progression, inhibiting cell death, and protecting against gamma radiation-induced DNA damage in RC cells. In conclusion, increased Paf15 expression is associated with increased RC proliferation, decreased patient survival, and a worse radiotherapeutic response.

MEG3/miR‑21 axis affects cell mobility by suppressing epithelial‑mesenchymal transition in gastric cancer

The prognosis of patients with gastric cancer remains poor mainly due to distant metastasis. Maternally expressed gene 3 (MEG3), a long non-coding RNA (lncRNA), is downregulated in various tumor tissues and suppresses tumor progression. miR-21 is a microRNA which is expressed highly in tumor tissues. In the present study, we investigated the relationship between MEG3 and miR-21 in regards to the cell mobility of gastric cancer. Our data demonstrated that MEG3 was downregulated while miR-21 was upregulated in gastric cancer tissues and cell lines by qRT-PCR. Overexpression of MEG3 suppressed cell mobility of gastric cancer cells (AGS) by downregulating the expression of MMP-3, MMP-9 and VEGF. As shown by western blot analysis, overexpression of MEG3 also suppressed epithelial-mesenchymal transition (EMT) by increasing the expression of an epithelial marker (E-cadherin) and downregulating the expression of mesenchymal markers (N-cadherin, Snail and β-catenin), indicating that MEG3 suppressed cell mobility through the inhibition of EMT in gastric cancer. The expression of miR-21 was negatively regulated by MEG3 and overexpression of miR-21 promoted cell mobility of AGS through activation of EMT. Co-transfection of lncRNA-MEG3 and miR-21 mimic counteracted the inhibitory effect on the cell mobility attributed to MEG3, suggesting that the MEG3/miR-21 axis affects cell mobility by suppressing EMT in gastric cancer. Using a mouse xenograft tumor model, we found that the overexpression of MEG3 suppressed tumor growth and metastasis while overexpression of miR-21 had the opposite effects. The MEG3/miR-21 axis affected gastric cancer growth and metastasis through inhibition of EMT in vivo. In conclusion, we demonstrated that the MEG3/miR-21 axis participates in the tumor progression and metastasis of gastric cancer through the regulation of EMT.

Downregulation of microRNA-4295 enhances cisplatin-induced gastric cancer cell apoptosis through the EGFR/PI3K/Akt signaling pathway by targeting LRIG1

Gastric cancer (GC) is one of the leading causes of cancer-associated mortality worldwide. The aim of the present study was to investigate the mechanism of microRNA-4295 (miR-4295), which regulates cisplatin (DDP)-induced apoptosis in GC cells through the leucinerich repeats and immunoglobulin-like domains 1 (LRIG1)-mediated epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Two cell lines were selected, one with the highest expression of miR-4295 and one with the lowest expression of LRIG1, for the experiments. The half maximal inhibitory concentration of DDP in the human GC MKN-28 and MKN-45 cell lines was calculated, and mitochondrial membrane potentials of the GC cells were detected by tetramethylrhodamine, ethyl ester, perchlorate staining. The proliferation and apoptosis of GC cells with or without DDP treatment were assessed by MTT assay and plate colony formation, as well as flow cytometry and TUNEL staining. Western blot analysis and reverse transcription-quantitative polymerase chain reaction were employed to determine the expression of EGFR/PI3K/Akt signaling pathway-related genes and apoptosis-related genes. LRIG1 was identified as a target gene of miR-4295. The expression of miR-4295 was upregulated, and the expression of LRIG1 was downregulated in GC cells. Furthermore, DDP enhanced the decrease in miR-4295 expression and the increase in LRIG1 expression in GC cells. miR-4295 promoted the proliferation and inhibited the DDP-induced apoptosis of GC cells without DDP treatment. In addition, miR-4295 increased the expression levels of EGFR, PI3K, Akt, p-PI3K and p-Akt, suggesting that miR-4295 promotes the activation of the EGFR/PI3K/Akt signaling pathway by targeting LRIG1. miR-4295 targeted and negatively regulated LRIG1 expression to activate the EGFR/PI3K/Akt signaling pathway, thereby promoting the proliferation of the GC cells and inhibiting the apoptosis of the GC cells induced by DDP. Therefore, miR-4295 may be a novel therapeutic target in patients with GC.