SNHG17 Serves as an Oncogenic lncRNA by Regulating the miR-361-3p/STC2 Axis in Rectal Cancer

Long noncoding RNA (lncRNA) have been reported to be crucial regulators for carcinogenesis, including rectal cancer. This work aimed to explore the roles and associated mechanisms of small nucleolar RNA host gene 17 (SNHG17) in rectal cancer. A quantitative real-time polymerase chain reaction was performed to measure the expression level of SNHG17 in rectal cancer tissues and cells. Cell counting kit-8 (CCK-8) assay and flow cytometry assay were conducted to measure the biological roles of SNHG17 in rectal cancer. In addition, luciferase activity reporter assay, RNA immunoprecipitation (RIP) assay, and rescue experiments were conducted to explore the mechanisms of SNHG17 in rectal cancer. The upregulation status of SNHG17 was identified in rectal cancer tissues and cells. Functionally, knockdown the expression of SNHG17 inhibits rectal cancer cell proliferation via stimulating cell apoptosis. In vivo assay showed that the knockdown of SNHG17 inhibits tumor growth. Furthermore, we showed that microRNA-361-3p (miR-361-3p) has decreased expression in tumor tissues and cells, and SNHG17 functions as a sponge for miR-361-3p. The upregulation status of stanniocalcin 2 (STC2) was also found in rectal cancer, and the knockdown of STC2 hinders cancer progression. In conclusion, lncRNA SNHG17 functions as an oncogenic lncRNA in rectal cancer by regulating the miR-361-3p/STC2 axis.

Stanniocalcin-2 promotes cell EMT and glycolysis via activating ITGB2/FAK/SOX6 signaling pathway in nasopharyngeal carcinoma

Stanniocalcin-2 (STC2) has been proved to regulate a variety of signaling pathways including cell growth, metastasis, and therapeutic resistance. However, the role of STC2 in the regulation of nasopharyngeal carcinoma (NPC) remains poorly understood. In this study, we investigated the regulatory function of STC2 on epithelial-mesenchymal transition (EMT) and glycolysis traits in NPC and revealed the underlying molecular mechanisms. We found that STC2 was highly expressed in primary nasopharyngeal carcinoma tissues and lymph node metastatic tissues. Silencing of STC2 inhibited cell proliferation, invasion, and glycolysis. Further analyses for the clinical samples demonstrated that STC2 expression was associated with the poor clinical progression. Moreover, we demonstrated the interaction of ITGB2 with STC2 and its involvement in STC2-mediated ITGB2/FAK/SOX6 axis. Collectively, our results provide new insights into understanding the regulatory mechanism of STC2 and suggest that the STC2/ITGB2/FAK/SOX6 signaling axis may be a potential therapeutic target for NPC.

Local IGF Bioactivity Associates with High PAPP-A Activity in the Pericardial Cavity of Cardiovascular Disease Patients

Objective Pregnancy-associated plasma protein-A (PAPP-A) has been suggested as a proatherogenic enzyme by its ability to locally increase insulin-like growth factor (IGF) activity through proteolytic cleavage of IGF binding protein-4 (IGFBP-4). Recently, stanniocalcin-2 (STC2) was discovered as an inhibitor of PAPP-A. This study aimed to investigate IGFBP-4, PAPP-A, and STC2 as local regulators of IGF bioactivity in the cardiac microenvironment by comparing levels in the pericardial fluid with those in the circulation of patients with cardiovascular disease. Methods Plasma and pericardial fluid were obtained from 39 patients undergoing elective cardiothoracic surgery, hereof 15 patients with type 2 diabetes. Concentrations of IGF-I, intact and fragmented IGFBP-4, PAPP-A, and STC2 were determined by immunoassays and IGF bioactivity by a cell-based assay. Results In pericardial fluid, the concentrations of total IGF-I, intact IGFBP-4, and STC2 were 72 ± 10%, 91 ± 5%, and 40 ± 24% lower than in plasma, while PAPP-A was 15 times more concentrated. The levels of the 2 IGFBP-4 fragments generated by PAPP-A and reflecting PAPP-A activity were elevated by more than 25%. IGF bioactivity was 62 ± 81% higher in the pericardial fluid than plasma. Moreover, pericardial fluid levels of both IGFBP-4 fragments correlated with the concentration of PAPP-A and with the bioactivity of IGF. All protein levels were similar in pericardial fluid from nondiabetic and diabetic subjects. Conclusions PAPP-A increases IGF bioactivity by cleavage of IGFBP-4 in the pericardial cavity of cardiovascular disease patients. This study provides evidence for a distinct local activity of the IGF system, which may promote cardiac dysfunction and coronary atherosclerosis.

CircRNA8220 Sponges MiR-8516 to Regulate Cell Viability and Milk Synthesis via Ras/MEK/ERK and PI3K/AKT/mTOR Pathways in Goat Mammary Epithelial Cells

Circular RNAs (circRNAs), which are considered a large class of endogenous noncoding RNAs, function as regulators in various biological procedures. In this study, the function and molecular mechanisms of circRNA8220 in goat mammary epithelial cells (GMECs) were explored. CircRNA8220 could spong miR-8516 and block the function of miR-8516 by binding to the target site of miR-8516 a negative feedback relationship existed between circRNA8220 and miR-8516. Stanniocalcin 2 (STC2) was a target gene of miR-8516. circRNA8220 could up-regulate the expression of STC2 by sponging miR-8516 in GMECs. circRNA8220/miR-8516/STC2 could promote proliferation and enhance the synthesis of β-casein and triglycerides (TG) via Ras/MEK/ERK and PI3K/AKT/mTOR signaling pathways, respectively.