LncRNA LY6E-DT and its encoded metastatic-related protein play oncogenic roles via different pathways and promote breast cancer progression.

Abnormal long noncoding RNA (lncRNA) expression plays an important role in tumor invasion and metastasis. Here, we show that lncRNA LY6E divergent transcript (LY6E-DT) levels are increased in breast cancer (BC) tissues. Transcription factor SP3 binds directly to the LY6E-DT promoter, activating its transcription. Moreover, LY6E-DT N6-methyladenosine modification by methyltransferase-like protein 14 (METTL14) promotes its expression, dependent on the "reader" insulin-like growth factor 2 mRNA binding protein 1(IGF2BP1)-dependent pathway. Notably, we discovered that the lncRNA LY6E-DT encodes a conserved 153-aa protein, "Metastatic-Related Protein" (MRP). Both LY6E-DT and MRP promote BC invasion and metastasis, and MRP expression could distinguish BC patients with lymph node metastasis from those without. Mechanistically, MRP binds heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC), enhancing the interaction between HNRNPC and epidermal growth factor receptor (EGFR) mRNA, increasing EGFR mRNA stability and protein expression and subsequently activating the phosphatidylinositol 3­kinase/protein kinase B signaling (PI3K) pathway. LncRNA LY6E-DT promotes the interaction between Y box binding protein 1 (YBX1) and importin α1 and increases YBX1 protein entry into the nucleus, where it transcriptionally activates zinc finger E-box-binding homeobox 1(ZEB1). Our findings uncover a novel regulatory mechanism underlying BC invasion orchestrated by LY6E-DT and its encoded MRP.

CAP2 promotes gastric cancer metastasis by mediating the interaction between tumor cells and tumor-associated macrophages.

The metastasis of cancer cells is the main cause of death in patients with gastric cancer (GC). Mounting evidence has demonstrated the vital importance of tumor-associated macrophages in promoting tumor invasion and metastasis; however, the interaction between tumor cells and macrophages in GC is largely unknown. In this study, we demonstrated that cyclase-associated protein 2 (CAP2) was upregulated in GC, especially in cases with lymph node metastasis, and was correlated with a poorer prognosis. The transcription factor JUN directly bound to the promoter region of CAP2 and activated CAP2 transcription. The N-terminal domain of CAP2 bound to the WD5 to WD7 domains of receptor for activated C kinase 1 (RACK1) and induced M2 macrophage polarization by activating the SRC/focal adhesion kinase (FAK)/ERK signaling pathway, which resulted in IL-4 and IL-10 secretion. Polarized M2 macrophages induced premetastatic niche formation and promoted GC metastasis by secreting TGFB1, which created a TGFB1/JUN/CAP2 positive-feedback loop to activate CAP2 expression continuously. Furthermore, we identified salvianolic acid B as an inhibitor of CAP2, which effectively inhibited GC cell invasion capabilities by suppressing the SRC/FAK/ERK signaling pathway. Our data suggest that CAP2, a key molecule mediating the interaction between GC cells and tumor-associated macrophages, may be a promising therapeutic target for suppressing tumor metastasis in GC.

Fabrication of a gel particle array in a microfluidic device for bioassays of protein and glucose in human urine samples.

This paper describes a simple method for fabricating a series of poly(ethylene glycol) diacrylate (PEG-DA) hydrogel microstructures inside microfluidic channels as probe for proteins and glucose. In order to demonstrate the feasibility of this newly developed system, bovine serum albumin (BSA) was chosen as a model protein. PEG microcolumns were used for the parallel detection of multiple components. Using tetrabromophenol blue (TBPB) and the horseradish peroxidase/glucose oxidase reaction system, bovine serum albumin (BSA) and glucose in human urine were detected by color changes. The color changes for BSA within a concentration range of 1-150 µM, and glucose within a range of 50 mM-2 M could be directly distinguished by eyes or precisely identified by optical microscope. To show the practicability of the gel particle array, protein and glucose concentrations of real human urine samples were determined, resulting in a good correlation with hospital analysis. Notably, only a 5 µL sample was needed for a parallel measurement of both analytes. Conveniently, no special readout equipment or power source was required during the diagnosis process, which is promising for an application in rapid point-of-care diagnosis.

A simple microfluidic chlorine gas sensor based on gas-liquid chemiluminescence of luminol-chlorine system.

In this work, a microfluidic chlorine gas sensor based on gas-liquid interface absorption and chemiluminescence detection was described. The liquid chemiluminescence reagent-alkaline luminol solution can be stably sandwiched between two convex halves of a microchannel by surface tension. When chlorine gas was introduced into the micro device, it was dissolved into the interfacial luminol solution and transferred to ClO(-), and simultaneously luminol was excited and chemiluminescence emitted. The emitted chemiluminescence light was perpendicularly detected by a photomultiplier tube on a certain detection region. The remarkable advantage of the detection system is that both adsorption and detection were carried out at the gas-liquid interface, which avoids the appearance of bubbles. The whole analytical cycle including filling CL reagent, sample injection, CL detection and emptying the device was as short as 30 s. The linear concentration range of chlorine gas detection with direct introduction of sample method is from 0.5 to 478 ppm. The detection limit of this method is 0.2 ppm for standard chlorine gas and the relative standard deviation of five determinations of 3.19 ppm spiked chlorine sample was 5.2%.