ABSTRACT
AIM: This study aims to investigate the potential role of lncRNA NR2F2-AS1 in the development of gastric cancer by affecting the levels of miR-320b and BMI1. BACKGROUND: Gastric cancer is a high-mortality malignancy, and understanding the underlying molecular mechanisms is crucial. Non-coding RNAs play an important role in gene expression, and their dysregulation can lead to tumor initiation and progression. OBJECTIVE: This study aims to determine the pathological role of LncRNA NR2F2-AS1 in gastric cancer progression and its association with the clinicopathological characteristics of patients. METHODS: Bioinformatics databases were used to predict the expression levels and interactions between the studied factors to achieve this objective. The expression pattern of NR2F2-AS1/miR- 320b/BMI1 in 40 pairs of tumor and adjacent normal tissues was examined using RT-PCR, IHC, and western blot. The correlation, ROC curve, and survival analyses were also conducted for the aforementioned factors. RESULTS: The results showed an increase of more than 2-fold for BMI-1 and lncRNA NR2F2-AS1 in lower stages, and the elevation continued with the increasing stage of the disease. This correlated with significant downregulation of miR-320b and PTEN, indicating their association with gastric cancer progression and decreased patient survival. LncRNA NR2F2-AS1 acts as an oncogene by influencing the level of miR-320b, altering the amount of BMI1. A reduction in the amount of miR-320b against lncRNA NR2F2-AS1 and BMI1 directly correlates with a reduced overall survival rate of patients, especially if this disproportion is more than 3.0. ROC curve analysis indicated that alteration in the lncRNA NR2F2-AS1 level showed more than 98.0% sensitivity and specificity to differentiate the lower from higher stages of GC and predict the early onset of metastasis. CONCLUSION: In conclusion, these results suggest that NR2F2-AS1/miR-320b/BMI1 has the potential to be a prognostic as well as diagnostic biomarker for gastric cancer.
ABSTRACT
AIMS: The role of SNHG4 in the initiation and development of gastric cancer. BACKGROUND: Gastric cancer is one of the leading causes of cancer death worldwide. Studies have shown that lncRNAs have a regulatory function in human diseases, particularly cancers. Small nuclear RNA host gene 4 (SNHG4) has been known as an oncogenic long noncoding RNA (lncRNA) in various cancers, and its dysregulation can lead to tumorigenesis and cancer progression. OBJECTIVE: Alteration of SNHG4 expression in gastric cancer and its correlation with clinical features of patients with stomach cancer; also, the accomplishment of bioinformatic analysis to find the potential pathways which could be impressed by changes in SNHG4 RNA expression. METHODS: The present study aims to determine the molecular mechanism of SNHG4 and the effects of its expression on the development of GC. Based on the bioinformatics investigations, we studied gene expression analysis, Kaplan-Meier survival, Gene ontology (GO), KEGG pathway enrichment, microRNA targets, transcription factor targets, and proteins interacting with SNHG4. During the experimental phase, SNHG4 expression was examined by quantitative real-time PCR (qRTPCR) in 40 paired gastric adenocarcinoma tissues and normal neighboring tissues. Also, we investigated the correlation between SNHG4 expression and patients' clinicopathological characteristics. RESULTS: Increased SNHG4 expression was detected in GC tissues, which is significantly associated with the TNM stage, grade group, tumor size, and metastatic status. Evaluation survival analysis demonstrated that overexpression of SNHG4 in GC tissues is remarkably related to poor overall survival (OS). SNHG4 is closely related to miR-490 and E2F family transcription factors. GO analysis suggested the possible role of SNHG4 in cell-cell adhesion, and KEGG enrichment analysis revealed that SNHG4 could be associated with the gastric cancer signaling pathway. ELAVL1 and IGF2BP2 have the highest number of SNHG4 target sites, and these proteins are involved in the PI3K-Akt-mTOR and ERK-MAPK signaling pathways. CONCLUSION: Based on our results, we conclude that SNHG4 may have a function in GC development by regulating tumor-related signaling pathways.
ABSTRACT
BACKGROUND: LncRNAs have been reported to be involved in a variety of biological functions, including gene expression, cell growth, and differentiation. They may also serve as oncogenes or tumor suppressor genes in diseases. lncRNAs that can encode small nucleolar RNAs (snoRNAs) have been named small nucleolar RNA host genes (SNHGs). OBJECTIVE: In this review article, we readily review the regulatory mechanisms and clinical significance of Lnc SNHG4 in cancer. METHODS: We systematically investigated databases, like Scopus, PubMed, Embase, Google Scholar, and Cochrane Library database for all research articles, and have provided an overview regarding the biological functions and mechanisms of lncRNA SNHG4 in tumorigenesis. RESULTS: Compared to neighboring normal tissues, SNHG4 is significantly dysregulated in various tumor tissues. SNHG4 upregulation is mainly associated with advanced tumor stage, tumor size, TNM stage, and decreased overall survival. In addition, aberrant SNHG4 expression promotes cell proliferation, metastasis, migration, and invasion of cancer cells. CONCLUSION: SNHG4 may serve as a new therapeutic target and prognostic biomarker in patients with cancer.
