Qu Cai

miR-126 functions as a tumour suppressor in human gastric cancer

MicroRNAs have emerged as important gene regulators and are recognised as key players in carcinogenesis. In the present study, we show that miR-126 was significantly down-regulated in gastric cancer tissues compared with matched normal tissues and was associated with clinicopathological features, including tumour size, lymph node metastasis, local invasion and tumour-node-metastasis (TNM) stage. Ectopic expression of miR-126 in SGC-7901 gastric cancer cells potently inhibited cell growth by inducing cell cycle arrest in G0/G1 phase, migration and invasion in vitro as well as tumorigenicity and metastasis in vivo. Mechanistically, we identified the adaptor protein Crk as a target of miR-126. Taken together, our results suggest that miR-126 may function as a tumour suppressor in gastric cancer, with Crk as a direct target.

MALAT1 promotes cell proliferation in gastric cancer by recruiting SF2/ASF.

The functions of long non-coding RNAs (lncRNAs) in gastric cancer (GC) remain largely unknown. MALAT1 is a kind of lncRNA that had been validated as a pivotal metastasis and prognosis mark in lung adenocarcinoma. In this study, we found that MALAT1 was aberrantly highly expressed in GC cell lines (SGC-7901, MKN-45 and SUN-16), and induced specific distribution and over-expression of SF2/ASF in nucleolus. Knock-down of MALAT1 or SF2/ASF in SGC-7901 cells respectively induced significant arrest of cell cycle in G0/G1 phase along with a remarkable suppression of cell proliferation, and the nuclear distribution and expression of SF2/ASF was significantly impaired when MALAT1 was depleted. However, over-expression of SF2/ASF exhibited no effect on rescuing the cell proliferation suppression by MALAT1 depletion. These results suggest that MALAT1 may function as a promoter of GC cell proliferation partly by regulating SF2/ASF, and our findings may provide us a likely biomarker and a potential target for GC diagnosis and therapeutic treatment.

Salinomycin can effectively kill ALDHhigh stem-like cells on gastric cancer

Salinomycin is a novel identified cancer stem cells (CSCs) killer. Higher ALDH activity represents CSCs characterization. Here, we screened ALDH activities on several gastric cancer cell lines and divided them into ALDH(high) and ALDH(low) gastric cancer groups. ALDH(high) cancer cells (NCI-N87 and SNU-1) disclosed more CSCs characteristics, such as higher levels of Sox2, Nanog and Nestin, more floating spheroid bodies, more colony formation and more resistance to conventional chemotherapeutic drugs 5-Fu and CDDP, compared to these parameters observed in ALDH(low) cancer cells (P<0.01). Importantly, ALDH(high) cancer cells are relatively sensitive to salinomycin when compared to ALDH(low) cancer cells (P<0.01). Our results confirmed ALDH as functional marker of CSCs population on gastric cancer. Salinomycin might be selective therapy for CSCs fraction, which is resistant to conventional anticancer drugs 5-Fu and CDDP.

MiRNA‐199a‐3p: A potential circulating diagnostic biomarker for early gastric cancer

Tumor‐associated miRNAs have been detected in serum or plasma. We investigated whether plasma miRNA‐199a‐3p could be a potential circulating biomarker for early gastric cancer (EGC).

Epigenetic silencing of microRNA-149 in cancer-associated fibroblasts mediates prostaglandin E2/interleukin-6 signaling in the tumor microenvironment

Tumor initiation and growth depend on its microenvironment in which cancer-associated fibroblasts (CAFs) in tumor stroma play an important role. Prostaglandin E2 (PGE2) and interleukin (IL)-6 signal pathways are involved in the crosstalk between tumor and stromal cells. However, how PGE2-mediated signaling modulates this crosstalk remains unclear. Here, we show that microRNA (miR)-149 links PGE2 and IL-6 signaling in mediating the crosstalk between tumor cells and CAFs in gastric cancer (GC). miR-149 inhibited fibroblast activation by targeting IL-6 and miR-149 expression was substantially suppressed in the CAFs of GC. miR-149 negatively regulated CAFs and their effect on GC development both in vitro and in vivo. CAFs enhanced epithelial-to-mesenchymal transition (EMT) and the stem-like properties of GC cells in a miR-149-IL-6-dependent manner. In addition to IL-6, PGE2 receptor 2 (PTGER2/EP2) was revealed as another potential target of miR-149 in fibroblasts. Furthermore, H. pylori infection, a leading cause of human GC, was able to induce cyclooxygenase-2 (COX-2)/PGE2 signaling and to enhance PGE2 production, resulting in the hypermethylation of miR-149 in CAFs and increased IL-6 secretion. Our findings indicate that miR-149 mediates the crosstalk between tumor cells and CAFs in GC and highlight the potential of interfering miRNAs in stromal cells to improve cancer therapy.

Epigenetic Silencing of miR-338-3p Contributes to Tumorigenicity in Gastric Cancer by Targeting SSX2IP

MicroRNA has been recently recognized as playing a prominent role in tumorigenesis and metastasis. Here, we report that miR-338-3p was epigenetically silenced in gastric cancer, and its down-regulation was significantly correlated with gastric cancer clinicopathological features. Strikingly, restoring miR-338-3p expression in SGC-7901 gastric cancer cells inhibited proliferation, migration, invasion and tumorigenicity in vitro and in vivo, at least partly through inducing apoptosis. Furthermore, we demonstrate the oncogene SSX2IP is a target of miR-338-3p. We propose that miR-338-3p functions as a tumor suppressor in gastric cancer, and the methylation status of its CpG island could serve as a potential diagnostic marker for gastric cancer.

Clinical significance of human kallikrein 10 gene expression in colorectal cancer and gastric cancer

Background and Aim:  Recent evidence suggests that the human kallikrein 10 (KLK10) gene is differentially regulated in endocrine‐related tumors and has potential as diagnostic and/or prognostic marker; however, KLK10 expression has never been investigated in gastrointestinal cancers. The aims of this study were to demonstrate expression and single nucleotide polymorphisms of KLK10 in colorectal cancer (CRC) and gastric cancer (GC), and to correlate the relative KLK10 expression level with clinicopathological factors of CRC and GC.

Proteomic identification of serum biomarkers for gastric cancer using multi-dimensional liquid chromatography and 2D differential gel electrophoresis

BACKGROUND Early diagnosis and treatment of gastric cancer patients is essential for improving prognosis. However, no available serum-based test provides sufficient sensitivity or specificity for widespread use. Therefore, in this study we aimed to identify cancer biomarkers in human sera using 2-dimensional difference gel electrophoresis (2D-DIGE), and to characterize protein biomarkers with tandem mass spectrometry. METHODS We compared the serum proteomic profiles of 20 gastric cancer patients and 10 healthy volunteers. Serum samples were first chromatographed using an immunoaffinity high-performance liquid chromatography (HPLC) column to selectively remove albumin, immunoglobulins, transferrin, haptoglobin, and antitrypsin. Differential protein analysis was then performed using DIGE. Significantly increased and decreased protein spot features were excised, trypsin digested, and analyzed by tandem matrix-assisted laser desorption/ionization (MALDI) time of flight (TOF)/TOF and a linear trap quadrupole (LTQ) mass spectrometer. RESULTS Seventeen protein spot features were significantly increased and 7 were significantly decreased in cancer serum samples compared to healthy controls. We identified 7 unique proteins that were upregulated, including plasminogen, apolipoprotein A-IV, Kininogen-1, complex-forming glycoprotein HC, complement component C4A, apolipoprotein J, and clusterin, and 5 that were decreased. CONCLUSIONS These results suggest that the combination of multi-dimensional HPLC and 2D-DIGE provides a valuable tool for serum proteomics in gastric cancer.

MiR-199a-3p promotes gastric cancer progression by targeting ZHX1

Accumulating evidence has indicated that microRNAs (miRNAs) act as critical epigenetic regulators in tumor carcinogenesis. Here, we report that miR‐199a‐3p was significantly upregulated in gastric cancer (GC) cell lines and tissues. Functional studies demonstrated that miR‐199a‐3p dramatically increased cell proliferation and suppressed cell apoptosis both in vitro and in vivo. Furthermore, the transcriptional regulator zinc fingers and homeoboxes 1 (ZHX1) was identified as one of the direct downstream targets of miR‐199a‐3p, miR‐199a‐3p bound to the ZHX1 3′ untranslated region (3′UTR) to regulate ZHX1 protein expression. In addition, the expression of miR‐199a‐3p was inversely associated with that of ZHX1 in GC cell lines. Overexpression of miR‐199a‐3p in SGC‐7901 cells inhibited ZHX1 expression, while reduction in miR‐199a‐3p by inhibitors in NCI‐N87 cells enhanced ZHX1 expression. Moreover, restoring ZHX1 expression in SGC‐7901/miR‐199a‐3p cells inhibited the cell proliferation induced by miR‐199a‐3p. Taken together, these findings suggest that miR‐199a‐3p may function as a novel tumor promoter in GC and its oncogenic activity may involve the direct targeting and inhibition of ZHX1.

A single-electron-transistor-based analog/digital converter

We propose a novel analog/digital (A/D) converter based on single-electron transistors (SETs) in this paper. In the proposed A/D converter, the core cell is a SET module, composed of capacitive dividers and SET-based universal literal gates. The SET-based universal literal gate is similar to the well-known Tuckers inverter (J.R. Tucker, J. Appl. Phys., vol. 72, no. 9, pp. 4399-4413, 1992), but here it acts as digital conversion and the inputs of upper-SET and lower-SET are two opposite voltages. In the SET-based universal literal gate, by adjusting the some parameters, the output having about 50% duty ratio of square-wave-like and zero-output for zero-input (in contrast, high-voltage output for zero-input in Tuckers inverter) is obtained, where we fully utilize the periodic oscillation of SETs on gate voltage (/spl I.bar/V/sub G/=e/C/sub G/). We demonstrate the basic function of a 4-bit SET-based A/D converter using the MOSES program developed by K.K. Likharevs group, which is based on the so-called orthodox theory and Monte Carlo method. The results may be easily extended to higher-bit A/D converters.