Overexpression of lncRNA TCLlnc1 in gastric cancer predicts postoperative distant recurrence and poor survival.

TCLlnc1 was characterized as a lncRNA with oncogenic roles in T cell lymphoma, whereas its role in other diseases is unknown. We then explored the involvement of TCLlnc1 in gastric cancer. Paired gastric cancer and nontumor tissues from 66 gastric cancer patients were used to extract total RNA samples, which were used to perform RT-qPCRs to determine the expression of TCLlnc1. Plasma samples from these 66 gastric cancer patients and 66 healthy controls were also used to detect circulating TCLlnc1. Correlations of TCLlnc1 in both plasma and tissue samples with patients' clinical data were analyzed by chi-square t -test. The diagnostic value of TCLlnc1 for early-stage gastric cancer was analyzed with the receiver operating characteristic curve. A 5-year follow-up study was performed to explore the prognostic value of TCLlnc1 for the survival of gastric cancer patients. TCLlnc1 expression in tissue was increased in gastric cancer. Plasma TCLlnc1 was also increased in gastric cancer. Plasma TCLlnc1 was closely correlated with TCLlnc1 in gastric cancer tissues, but not TCLlnc1 in nontumor tissues. TCLlnc1 in plasma was only correlated with tumor distant metastasis, but not other clinical data. TCLlnc1 in plasma showed promising diagnostic value for stage I and II gastric cancer. Increased accumulation of TCLlnc1 was closely correlated with distant recurrence and poor survival during a 5-year follow-up. Therefore, TCLlnc1 is overexpressed in gastric cancer predicts postoperative distant recurrence and poor survival.

miR-144-3p inhibited the growth, metastasis and epithelial-mesenchymal transition of colorectal adenocarcinoma by targeting ZEB1/2.

miR-144-3p is aberrantly expressed in several types of human cancer and functions as a tumor suppressor by inhibiting metastasis. However, the clinical significance and biological function of miR-144-3p in colorectal adenocarcinoma (CRA) have yet to be elucidated. Here we reported that miR-144-3p expression level was significantly down-regulated in CRA tissues compared with matched noncancerous colorectal mucosae tissues. Low miR-144-3p expression was correlated with adverse clinicopathologic characteristics and poor prognosis of CRA patients. Cox regression analysis showed that low miR-144-3p expression was an independent risk factor for DFS and OS in CRA. In vitro and in vivo assays showed that miR-144-3p significantly inhibited proliferation, migration and invasion of CRA cells. In particular, miR-144-3p could suppress EMT process of CRA cells by regulating the cytoskeleton and EMT markers. Bioinformatics analysis indicated that EMT associated transcription factors ZEB1 and ZEB2 were potential targets of miR-144-3p, and miR-144-3p inhibited ZEB1 and ZEB2 expression and was negatively correlated with their expression in CRA. Finally, we confirmed that ZEB1 and ZEB2 down-regulation collaboratively mediated the inhibitory effect of miR-144-3p on proliferation, invasion and EMT of CRA cells. In conclusion, our study provided evidence that miR-144-3p could inhibit CRA cell proliferation, invasion and EMT by targeting ZEB1/2.

WDR1 predicts poor prognosis and promotes cancer progression in hepatocellular carcinoma.

WDR1, an activator of cofilin-mediated actin depolymerization, is involved in various actin-dependent processes of living cells including cell migration and cytokinesis. Recently, several studies have found that WDR1 is dysregulated in several types of cancer and is associated with cancer metastasis. However, its role in hepatocellular carcinoma (HCC) remains unknown. In this study, we found that WDR1 expression was aberrantly upregulated at the mRNA and protein levels in HCC cell lines and HCC tissues. WDR1 overexpression was highly correlated with tumor aggressive phenotypes such as capsulation formation, microvascular invasion (MVI), tumor node metastasis (TNM) stage, and was an independent poor prognostic factor for overall survival (OS) and disease-free survival (DFS) for HCC patients after curative surgery. Furthermore, WDR1 overexpression significantly promoted HCC cell migration, invasion and proliferation. In contrast, WDR1 downregulation inhibited HCC cell migration, invasion and proliferation. Conclusion: This study indicates that WDR1 could be used as a new useful prognostic marker and may be a potential therapeutic target for HCC.

ARHGEF7 promotes metastasis of colorectal adenocarcinoma by regulating the motility of cancer cells.

Previous studies have shown that Rho guanine nucleotide exchange factor 7 (ARHGEF7) is implicated in cytoskeleton remodelling, which is important for cell motility and invasiveness, and exhibits frequent high-level genetic amplification in metastatic lesions of colorectal adenocarcinoma. Therefore, it was hypothesized that ARHGEF7 may be involved in the metastasis of colorectal adenocarcinoma. In the present study, it was demonstrated that the expression level of ARHGEF7 was significantly upregulated in colorectal adenocarcinoma tumor tissues compared with matched nontumorous tissues, and its expression level correlated with colorectal adenocarcinoma metastasis. In vitro assays showed that the overexpression of ARHGEF7 in CRC cells significantly enhanced cell migration and invasion, whereas the knockdown of ARHGEF7 in colorectal adenocarcinoma cells significantly decreased cell migration and invasion. In vivo assays showed that the overexpression of ARHGEF7 in CRC cells facilitated tumor metastasis, whereas the knockdown of ARHGEF7 in CRC cells significantly inhibited tumor metastasis. Furthermore, it was demonstrated that ARHGEF7 promoted cell motility by regulating the actin cytoskeleton. Finally, according to ReMARK guidelines for reporting prognostic biomarkers in cancer, it was found that a high expression of ARHGEF7 was significantly correlated with lymph node, mesenteric and distant metastasis. Patients with colorectal adenocarcinoma with a high expression of ARHGEF7 had shorter disease-free survival (DFS) and shorter overall survival (OS) rates, compared with those with a low expression of ARHGEF7, as determined by the Kaplan-Meier method with a log-rank test. Cox regression analysis showed that a high expression of ARHGEF7 was an independent risk factor for DFS and OS rates in colorectal adenocarcinoma.