Identification of combinatorial miRNA panels derived from extracellular vesicles as biomarkers for esophageal squamous cell carcinoma.

MicroRNAs (miRNAs) are relatively stable in blood, emerging as one of the most promising biomarkers in tumor liquid biopsy. Both total and extracellular vesicles (EVs) encapsulated miRNA have been studied for prognostic potential in a variety of cancers. Here, we systematically compared and verified the total and vesicle-derived miRNA expression profiles from plasma samples in healthy controls and patients with esophageal squamous cell carcinoma (ESCC). In the present study, four miRNA species miR-636, miR-7641, miR-28-3p, and miR-1246 that were differentially expressed in ESCC patients were chosen for further study. We first elucidated their essential function in ESCC progression and further explored their preliminary mechanism by identifying target proteins and involving signal pathways. Subsequently, the prognostic miRNA panels including miR-636, miR-7641, miR-1246, and miR-28-3p for ESCC diagnosis were constructed and validated using different cohort. Our results showed that the panel including the above four miRNAs derived from plasma EVs was most effective in distinguishing tumor patients from normal subjects, while integrated plasma EVs-derived miR-1246, miR-28-3p and total plasma miRNAs miR-636, miR-7641 showed the best capability in predicting lymph node metastasis. In summary, our studies revealed that plasma EVs-derived miRNAs could be emerged as promising biomarkers for ESCC diagnosis.

Dual-emission carbon dots-stabilized copper nanoclusters for ratiometric and visual detection of Cr2O72- ions and Cd2+ ions.

The pollution of heavy metal increases greatly accompanying by the development of industries. So, it is very important to build up a quick and reliable technique for detection of heavy metal ions. In this work, we developed a simple and convenient method for ratiometric and visual detection of Cr2O72- ions and Cd2+ ions. We utilized glutathione as raw material to prepare cyan-emitting carbon dots (GSH@CDs). The GSH@CDs were further used as the template to prepare carbon dots-stabilized copper nanoclusters (GSH@CDs-Cu NCs) that displayed two well-separated emission peaks respectively at 450 nm and 750 nm. The GSH@CDs-Cu NCs can be applied for the ratiometric and visual detection of Cr2O72- and Cd2+ ions based on the fluorescence quenching or enhancement of GSH@CDs-Cu NCs at 750 nm. A linear range of 2-40 µmol L-1 with a detection limit of 0.9 µmol L-1 for Cr2O72- ions, and a linear range of 0-20 µmol L-1 with a detection limit of 0.6 µmol L-1 for Cd2+ ions were achieved based on this method. The fluorescent test strips for Cr2O72- ions were successfully prepared based on GSH@CDs-Cu NCs. Moreover, the GSH@CDs-Cu NCs were successfully applied to determine Cr2O72- and Cd2+ ions in real samples with promising results.

Knockdown of ISOC1 inhibits the proliferation and migration and induces the apoptosis of colon cancer cells through the AKT/GSK-3ß pathway.

Isochorismatase domain-containing 1 (ISOC1) is a coding gene that contains an isochorismatase domain. The precise functions of ISOC1 in humans have not been clarified; however, studies have speculated that it may be involved in unknown metabolic pathways. Currently, it is reported that ISOC1 is associated with breast cancer. In this research, the aim is to investigate the critical role of ISOC1 in colorectal cancer (CRC) and to explore its biological function and mechanism in colon cancer cells. In 106 paired clinical samples, we found that the levels of ISOC1 expression were widely increased in cancer tissues compared with matched adjacent non-tumor tissues and that increased expression of ISOC1 was significantly associated with tumor size, tumor invasion, local lymph node metastasis and Tumor, Node and Metastasis (TNM) stage. Moreover, higher expression levels of ISOC1 were correlated with shorter disease-free survival in patients 2 years after surgery. In vitro, ISOC1 knockdown inhibited the proliferation and migration and induced the apoptosis of colon cancer cells, and in vivo, the xenograft tumors were also inhibited by ISOC1 silencing. We also used MTS, Transwell and cell apoptosis assays to confirm that ISOC1 plays a critical role in regulating the biological functions of colon cancer cells through the AKT/GSK-3ß pathway. Additionally, the results of confocal microscopy and western blot analysis indicated that ISOC1 knockdown could promote p-STAT1 translocation to the nucleus.

The tumor-suppressive function of miR-1296-5p by targeting EGFR and CDK6 in gastric cancer.

We aimed to confirm the role of miR-1296-5p in gastric cancer and to identify its target genes. The expression of miR-1296-5p was measured in gastric cancer tissues and cell lines. The function of miR-1296-5p was examined by the overexpression and inhibition of its expression in typical gastric cell lines as well as SGC-7901 and MGC-803 cells. The targets of miR-1296-5p were identified by a luciferase activity assay. We found that miR-1296-5p was down-regulated in gastric cancer tissue and cell lines, and low expression levels of miR-1296-5p were associated with advanced clinical stage. Moreover, miR-1296-5p inhibited cell proliferation, migration, and invasion in SGC-7901 and MGC-803 cells. Then, we identified CDK6 and EGFR as novel targets of miR-1296-5p by a luciferase activity assay. Furthermore, the overexpression of miR-1296-5p suppressed the expression of CDK6 and EGFR. Our results indicated a tumor-suppressive role of miR-1296-5p through the translational repression of oncogenic CDK6 and EGFR in gastric cancer.