DARS-AS1 modulates cell proliferation and migration of gastric cancer cells by regulating miR-330-3p/NAT10 axis

Abstract

The long noncoding RNA DARS-AS1 was aberrantly expressed and participated in several human cancer progressions, whereas whether DARS-AS1 is involved in human gastric cancer remains unclear. This study aimed to investigate the influence of DARS-AS1 on gastric cancer progression and explore the potential regulatory network of DARS-AS1/miR-330-3p/NAT10. The expression levels of DARS-AS1, miR-330-3p, and NAT10 were measured by quantitative real-time polymerase chain reaction. The CCK-8 assay and Transwell assay were used to determine the cell viability, migration, and invasion capacities, respectively. The target association between miR-330-3p and DARS-AS1 or NAT10 was confirmed using a luciferase reporter assay. In result, DARS-AS1 levels were elevated in tumor tissues and associated with shorter overall survival in patients with gastric cancer. Knockdown of DARS-AS1 could hamper cell viability, migration, and invasion in gastric cancer cells. DARS-AS1 acts as a competitive endogenous RNA to regulate the NAT10 expression by sponging miR-330-3p in gastric cancer cells. In conclusion, DARS-AS1 was elevated in gastric cancer, and DARS-AS1/miR-330-3p/NAT10 signaling offered some new horizons for predicting prognosis and a novel therapeutic method for the treatment of gastric cancer.

DARS-AS1: A Vital Oncogenic LncRNA Regulator with Potential for Cancer Prognosis and Therapy

“…Several investigations have explored the relationship between DARS-AS1 expression and clinicopathological characteristics across a spectrum of five tumor types ( Table 1 ). In gastric cancer 51 , DARS-AS1 exhibits a significant positive correlation with T category, N category, TNM stage. In hepatocellular carcinoma 35 , overexpression DARS-AS1 indicates larger tumor size and advanced TNM stage.…”

“…ensembl.org/Homo_sapiens/Gene/Summary?g = ENSG00000231890; r = 2:135985124-136022593). As an antisense lncRNA, DARS-AS1 has emerged as a recognized oncogenic entity, implicated in a wide array of cancer types as supported by extensive research publications [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51], as depicted in Figure 1. These encompass cancers originating from various organ systems, including the digestive, urinary, respiratory, female reproductive, hematological, and neurological systems, among others.…”

“…Spanning 22,367 nucleotides and comprising five exons (source: https://www.ncbi.nlm.nih.gov/gene/101928243 ), DARS-AS1 gives rise to a remarkable 34 splice variants, ranging in size from 311 base pairs for DARS1-AS1-228 to 1634 base pairs for DARS1-AS1-233(source: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g = ENSG00000231890; r = 2:135985124-136022593). As an antisense lncRNA, DARS-AS1 has emerged as a recognized oncogenic entity, implicated in a wide array of cancer types as supported by extensive research publications 33 - 51 , as depicted in Figure 1 . These encompass cancers originating from various organ systems, including the digestive, urinary, respiratory, female reproductive, hematological, and neurological systems, among others.…”

“…In the case of DARS-AS1, its ceRNA network encompasses eight miRNAs across nine different types of cancers, as illustrated in Figure 4 . These miRNAs include miR-330-3p in gastric cancer 51 , miR-3200-5p in hepatocellular carcinoma 35 , miR-194-5p in clear cell renal cell carcinoma 36 and ovarian cancer 38 , 48 , miR-188-5p in lung adenocarcinoma 42 and cervical cancer 49 , miR-532-3p in non-small cell lung cancer 39 and osteosarcoma 45 , miR-129-2-3p in triple-negative breast cancer 40 , miR-628-5p in cervical cancer 33 , and miR-425 in childhood acute myeloid leukemia 34 .…”