Background. Long noncoding RNAs (lncRNAs) were recently shown to have potential in the diagnosis and prognosis for numerous cancers. lncRNA GAS8-AS1 is decreased in papillary thyroid cancer (PTC) tissue, but its plasma expression and clinical value in patients with PTC remain unknown. Materials and Methods. We investigated the expression profile of plasma GAS8-AS1 in 97 patients with PTC and 39 patients with nodular goiter by quantitative real-time polymerase chain reaction. Results. GAS8-AS1 expression in plasma was downregulated in patients with PTC in comparison with those in nodular goiters (P<0.001). A low level of plasma GAS8-AS1 expression was correlated with lymph node metastasis (LNM) (P<0.001). Multivariate analysis showed that a reduced GAS8-AS1 level in plasma was associated with LNM (P<0.05). The area under the receiver operating characteristic curve for GAS8-AS1 was 0.746 in LNM prediction (P<0.001). Conclusion. The present study indicates that circulating GAS8-AS1 is a potential biomarker for PTC diagnosis and LNM prediction.

Helicobacter pylori (H. pylori) is designated as a class I carcinogen of human gastric cancer after a long-term infection. During this process, H. pylori persists in proliferation and death, releases bacterial components, which contact with gastric epithelial cells and regulate cell function. However, the long-term treatment of H. pylori lysate in the pathological changes of gastric cells is not clear. In this study, GES-1 and MKN-45 cells were treated with H. pylori lysate for 30 generations, and cells proliferation, migration, invasion, autophagy and apoptosis were detected to determine the regulation of cell by continuous exposure to lysate. Furthermore, Mongolian gerbils were infected by H. pylori ATCC 43504 strains for 90 weeks to verify the results in vitro. We found that sustained exposure to H. pylori lysate inhibited host cells invasion, migration, autophagy and apoptosis. The clinical data and in vitro showed that the expression changes of Nod1, NF-κB, MAPK/ERK and FOXO pathways and the downstream genes related to apoptosis and autophagy. Sustained exposure to H. pylori lysate inhibited cells apoptosis and autophagy through Nod1-NF-κB/MAPK-ERK/FOXO4 signaling pathway. In conclusion, sustained exposure to H. pylori lysate promoted proliferation of gastric epithelial cells and inhibited autophagy and apoptosis through Nod1-NF-κB/MAPK-ERK/FOXO4 signaling pathway.

Focal adhesion kinase (FAK) is highly expressed in a variety of human cancers and is a target for cancer therapy. Since FAK kinase inhibitors only block the kinase activity of FAK, they are not highly effective in clinical trials. FAK also functions as a scaffold protein in a kinase-independent pathway. To effectively target FAK, it is required to block both FAK kinase-dependent and FAK-independent pathways. Thus, we tested a new generation drug FAK PROTAC for ovarian cancer therapy, which blocks both kinase and scaffold activity. We tested the efficacy of FAK PROTAC and its parent kinase inhibitor (VS-6063) in ovarian cancer cell lines in vitro by performing cell functional assays including cell proliferation, migration, invasion. We also tested in vivo activity in orthotopic ovarian cancer mouse models. In addition, we assessed whether FAK PROTAC disrupts kinase-dependent and kinase-independent pathways. We demonstrated that FAK PROTAC is highly effective as compared to its parent FAK kinase inhibitor VS-6063 in inhibiting cell proliferation, survival, migration, and invasion. FAK PROTAC not only inhibits the FAK kinase activity but also FAK scaffold function by disrupting the interaction between FAK and its interaction protein ASAP1. We further showed that FAK PROTAC effectively inhibits ovarian tumor growth and metastasis. Taken together, FAK PROTAC inhibits both FAK kinase activity and its scaffold protein activity by disrupting the interaction between FAK and ASAP1 and is highly effective in inhibiting ovarian tumor growth and metastasis.

Long noncoding RNAs (lncRNAs) are involved in diabetes related diseases. However, the role of lncRNAs in the pathogenesis of type 2 diabetes with macrovascular complication (DMC) has seldomly been recognized. This study screened lncRNA profiles of leukocytes from DMC patients and explored protective role of lncRNA LYPLAL1-DT in endothelial cells (EC) under high glucose (HG) and inflammatory conditions (IS). Between DMC and healthy controls, 477 differential expression lncRNAs (DE-lncRNAs) were identified. The enrichment and pathway analysis showed that most of the DE-lncRNAs belonged to inflammatory, metabolic, and vascular diseases. A total of 12 lncRNAs was validated as significant DE-lncRNAs in expanding cohorts. Furthermore, these DE-lncRNAs were shown to be significantly related to hypoxia, HG, and IS in EC, especially lncRNA LYPLAL1-DT. LYPLAL1-DT overexpression results in the promotion of the proliferation, and migration of EC, as well as an elevation of autophagy. Overexpressed LYPLAL1-DT reduces the adhesion of monocytes to EC, boosts anti-inflammation, and suppresses inflammatory molecules secreted in the medium. Mechanistically, LYPLAL1-DT acts as competing endogenous RNA (ceRNA) by downregulating miR-204-5p, therefore enhancing SIRT1 and protecting EC autophagy function; thus, alleviating apoptosis. Finally, exosome sequencing revealed LYPLAL1-DT expression was 4 times lower in DMC cells than in healthy samples. In general, we identified LYPLAL1-DT having protective effects on EC as ceRNA mediated through the miR-204-5p/SIRT1 pathway. Therefore, it inhibits the autophagy of EC as well as modulating systemic inflammation. This approach could be regarded as a new potential therapeutic target in DMC.