Downregulation of LncRNA DARS-AS1 Inhibits the Tumorigenesis of Cervical Cancer via Inhibition of IGF2BP3

Abstract

Background Evidence has been shown that long noncoding RNAs (lncRNAs) play an important role in the development of cervical cancer. Recently, lncRNA DARS-AS1 was reported to be dysregulated in several cancer types; however, the role of DARS-AS1 in cervical cancer remains unclear. Methods Flow cytometry and transwell invasion assays were performed to determine the apoptosis and invasion in cervical cancer cells. In addition, RNA pull-down and fluorescence in situ hybridization (FISH) assays were conducted to assess the interaction between DARS-AS1 and IGF2BP3 in cervical cancer cells. Results Downregulation of DARS-AS1 significantly induced apoptosis and cell cycle arrest in cervical cancer cells. Meanwhile, the invasion ability of cervical cancer cells was inhibited by DARS-AS1 knockdown as well. RNA pull-down and FISH results showed that DARS-AS1 interacted with IGF2BP3. Mechanistically, DARS-AS1 positively regulated IGF2BP3 expression via stabilization of IGF2BP3 mRNA. Rescue assays confirmed that DARS-AS1 regulated the progression of cervical cancer through interacting with IGF2BP3 in vitro. In addition, in vivo experiments revealed that downregulation of DARS-AS1 inhibited tumor growth in SiHa xenograft model. Conclusion In this study, we found that downregulation of DARS-AS1 could inhibit the growth of cervical cancer cells via inhibition of IGF2BP3, suggesting DARS-AS1 might serve as a potential target for the treatment of cervical cancer.

lncRNA DARS-AS1 Modulates TSPAN1-Mediated ITGA2 Hypomethylation by Interaction with miR-194-5p Thus Promoting Ovarian Cancer Progression

“…Although the function role of DARS-AS1 has been extensively investigated in various malignant tumors, such as renal cell carcinoma [ 14 ], hepatocellular carcinoma [ 34 ], and thyroid cancer [ 35 ], insufficient evidence has been shown to conclude its potential mechanism acting on OC. According to the results of the GEPIA 2 database and qRT-PCR, we found that compared to normal ovarian tissues and human normal ovarian epithelial cell line, the OC tissues and OC cell lines showed elevated lncRNA DARS-AS1 expression, which was supported by other studies [ 36 , 37 ]. A2780 is a human epithelial OC cell line isolated from untreated females with OC, with strong migration and invasion ability due to its weak adhesion to the matrix membrane.…”

Systems Biomedicine of Primary and Metastatic Colorectal Cancer Reveals Potential Therapeutic Targets

“…This gene encodes a member of a multi-enzyme complex that its role has been proved in mediating attachment of amino acids to their cognate tRNAs. Some studies have reported that DARS-AS1 gene (encoding a long noncoding RNA) act as an oncogene ( 98 ) and is positively associated with the pathological stages in thyroid and ovarian cancer by targeting mir-129 and mir-532-3p, respectively ( 99 , 100 ). Moreover, this gene is directly upregulated by HIF1 gene, which stabilizes RBM39 protein in Myeloma ( 101 ).…”

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

“…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.…”