Purpose Alzheimer's disease (AD) is the most common neurodegenerative disease, with a rising prevalence worldwide. Long noncoding RNAs (lncRNAs) have been found to play important roles in the development and treatment of AD. However, the exact role of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in neuronal damage in AD is largely unknown. Materials and Methods The AD model was established in SH-SY5Y and SK-N-SH cells via treatment with amyloid β 1−42 (Aβ). The expression of NEAT1 and microRNA-107 (miR-107) was measured by quantitative real-time polymerase chain reaction. Cell viability and apoptosis were detected by MTT assay, immunocytochemistry, and flow cytometry. The expression of phosphorylated tau protein (p-Tau) was measured by Western blot. The interaction between NEAT1 and miR-107 was explored by bioinformatics analysis, luciferase activity, and RNA immunoprecipitation assays. Results NEAT1 expression was enhanced in Aβ-treated SH-SY5Y and SK-N-SH cells, and its knockdown attenuated Aβ-induced inhibition of viability and promotion of apoptosis and p-Tau levels. NEAT1 was indicated as a decoy of miR-107. miR-107 abundance was reduced in Aβ-treated cells, and its overexpression reversed Aβ-induced injury. Moreover, interference of miR-107 abated silencing of NEAT1-mediated inhibition of neuronal damage in Aβ-treated SH-SY5Y and SK-N-SH cells. Conclusion LncRNA NEAT1 aggravated Aβ-induced neuronal damage by sponging miR-107, indicating a novel avenue for treatment of AD.

Elk-1, a c-Fos protooncogene regulator, which belongs to the ETS-domain family of transcriptional factors, plays an important role in the induction of immediate early gene expression in response to a variety of extracellular signals. In this study, we demonstrate for the ®rst time the in vitro and in vivo interaction of Elk-1 with BRCA1 splice variants BRCA1a and BRCA1b using GST-pull down assays, co-imunoprecipitations/Western blot analysis of cell extracts from breast cancer cells and mammalian two-hybrid assays. We have localized the BRCA1 interaction domain of Elk-1 protein to the conserved ETS domain, a motif involved in DNA binding and protein ± protein interactions. We also observed binding of BRCA1 proteins to other ETS-domain transcription factors SAP1, ETS-1, ERG-2 and Fli-1 but not to Elk-1 splice variant DElk-1 and c-Fos protooncogene. Both BRCA1a and BRCA1b splice variants function as growth suppressors of human breast cancer cells. Interestingly, our studies reveal that although both Elk-1 and SAP-1 are highly homologous members of a subfamily of ETS domain proteins called ternary complex factors, it is only Elk-1 but not SAP-1 that can augment the growth suppressive function of BRCA1a/1b proteins in breast cancer cells. Thus Elk-1 could be a potential downstream target of BRCA1 in its growth control pathway. Furthermore, we have observed inhibition of c-Fos promoter activity in BRCA1a transfected stable breast cancer cells and over expression of BRCA1a/1b attenuates MEK-induced SRE activation in vivo. These results demonstrate for the ®rst time a link between the growth suppressive function of BRCA1a/1b proteins and signal transduction pathway involving Elk-1 protein. All these results taken together suggest that one of the mechanisms by which BRCA1a/1b proteins function as growth/tumor suppressors is through inhibition of the expression of Elk-1 target genes like c-Fos.

MIE in the lateral-prone position is technically less demanding and provides better technical safety, with good oncological effectiveness. This positioning is a feasible and appropriate alternative for minimally invasive surgery of esophageal carcinoma.

Low‐intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, was recently demonstrated to be an effective treatment for osteoarthritis (OA). Vascular endothelium growth factor A (VEGFA) has been found to be upregulated in the articular cartilage, synovium and subchondral bone of OA patients, leading to cartilage degeneration, synovitis and osteophyte formation. However, the functions and mechanisms of LIPUS in regulating chondrocyte‐derived VEGFA expression are still unclear. In this study, we investigated whether LIPUS attenuated OA progression by (a) decreasing the percentage of VEGFA‐positive cells in mouse articular cartilage destabilised through medial meniscus surgery and (b) relieving interleukin‐1β‐induced VEGFA expression in mouse primary chondrocytes. However, this function was negated by a p38 mitogen‐activated protein kinase (p38 MAPK) inhibitor. In addition, we found that LIPUS ameliorated VEGFA‐mediated disorders in cartilage extracellular matrix metabolism and chondrocyte hypertrophy during OA development. In conclusion, our data indicate a novel effect of LIPUS in regulating the expression of osteoarthritic chondrocyte‐derived VEGFA through the suppression of p38 MAPK activity.

Human melanoma is a highly malignant tumor originating from cutaneous melanocytes. The noncoding RNA microRNA (miR)‐21‐5p has been reported to be expressed at high levels in malignant melanocytic skin tissues, but its potential functional role in melanoma remains poorly understood. Here, we explored the cellular effects of miR‐21‐5p on melanoma in vitro and the underlying mechanisms. Quantitative real‐time PCR was used to show that miR‐21‐5p is significantly up‐regulated in clinical samples from patients with melanoma as compared with adjacent noncancerous tissues. Overexpression of miR‐21‐5p significantly enhanced, whereas knockdown attenuated, cell proliferation and G1/S transition in melanoma cell lines (A375 and M14). Luciferase reporter assays were used to show that the cyclin‐dependent kinase inhibitor 2C (CDKN2C) is a downstream target of miR‐21‐5p. Furthermore, miR‐21‐5p mimics resulted in a decrease in CDKN2C expression, and CDKN2C expression was observed to be inversely correlated with miR‐21‐5p expression in melanoma tissues. Rescue experiments were performed to show that overexpression of CDKN2C partially reversed the effects of miR‐21‐5p up‐regulation on A375 cells. Consistently, knockdown of CDKN2C abolished the effects of miR‐21‐5p down‐regulation on A375 cells. Overall, our studies demonstrate that miR‐21‐5p can promote the growth of melanoma cells by targeting CDKN2C, which may induce G0/G1 phase arrest of melanoma cells.