IncRNA BG981369 Inhibits Cell Proliferation, Migration, and Invasion, and Promotes Cell Apoptosis by SRY-Related High-Mobility Group Box 4 (SOX4) Signaling Pathway in Human Gastric Cancer
MEDICAL SCIENCE MONITOR
Authors: Dong, Xiuli; Chen, Renpin; Lin, Haihua; Lin, Tiesu; Pan, Shuang
Abstract
Background: Human gastric cancer (GC) is a leading primary cause of cancer-associated deaths in both males and females worldwide. However, there are few effective diagnostic and therapeutic measures for GC patients due to the complicated underlying mechanisms of GC. Recently, increasing research has indicated that lncRNAs may play a critical role in the progression of GC. Material/Methods: AI769947, AK054978, DB077273, BG981369, AK054588, and AF131784 expressions were analyzed by qRT-PCR assay in GC tissues and corresponding normal tissues (n=44). BG981369 expression was detected by qRT-PCR assay in GC cells. BG981369 was overexpressed and silenced in AGS and SNU-5 cells. The proliferation ability was detected by MTT and colony formation assays. Cell cycle distribution and cell apoptosis rate were analyzed by flow cytometry. The migration and invasion abilities were measured by Transwell assay. In addition, SOX4 expression was analyzed by qRT-PCR in GC tissues. The correlation between SOX4 and BG981369 was analyzed by Pearson analysis. Results: The results indicated that lncRNA BG981369 was significantly higher in GC tissues than in normal tissues. Overexpression of BG981369 inhibited the proliferation, migration, and invasion and promoted apoptosis of gastric adenocarcinoma (AGS) cells, and silencing of BG981369 promoted proliferation, migration, and invasion, and inhibited cell apoptosis of SNU-5 cells. Furthermore, we found that SOX4 may act as a downstream mediator of BG981369, suggesting that BG981369 inhibits proliferation, migration, and invasion, and promotes apoptosis by targeting SOX4 in the GC cell lines. Conclusions: Our results suggest that BG981369 and SOX4 are potentially effective therapeutic targets for GC.
RNA sequencing uncovers the key long non-coding RNAs and potential molecular mechanism contributing to XAV939-mediated inhibition of non-small cell lung cancer
ONCOLOGY LETTERS
Authors: Yu, Haixiang; Han, Zhifeng; Xu, Zhenan; An, Chong; Xu, Lei; Xin, Hua
Abstract
The present study aimed to reveal the key long non-coding RNAs (lncRNAs) and the potential molecular mechanisms of XAV939 treatment in non-small cell lung cancer (NSCLC). The NSCLC cell line, NCI-H1299, was cultured with 10 mu M XAV939 for 12 h, and NCI-H1299 cells without XAV939 treatment were used as controls. Following RNA isolation from the two groups, RNA-sequencing was performed to detect transcript expression levels, and differentially-expressed lncRNAs (DE-lncRNAs) and DE-genes (DEGs) were identified between groups and analyzed for their functions and associated pathways. The potential associations between proteins encoded by DEGs were revealed via a protein-protein interaction (PPI) network. Subsequently, the microRNA (miRNA/miR)-mRNA, lncRNA-miRNA and lncRNA-mRNA interactions were explored, followed by competing endogenous RNA (ceRNA) network construction. A total of 396 DEGs and 224 DE-lncRNAs were identified between the XAV939 and control groups. These lncRNAs were mainly enriched in pathways such as ferroptosis' [DEG, solute carrier family 7 member 11 (SLC7A11)]. The PPI network consisted of 97 nodes and 112 interactions. Furthermore, a total of 10 noteworthy lncRNAs were revealed in the DE-lncRNA-DEG interaction. Finally, the lncRNA-miRNA-mRNA regulatory association, including MIR503 host gene (MIR503HG)-miR1273c-SRY-box 4 (SOX4), was explored in the current ceRNA network. The downregulation of lncRNA MIR503HG induced by XAV939 may serve an important role in NSCLC suppression via sponging miR-1273c and regulating SOX4 expression. Furthermore, the downregulation of SLC7A11 induced by XAV939 may also inhibit the development of NSCLC via the ferroptosis pathway.