EIF4A3‐mediated hsa_circ_0088088 promotes the carcinogenesis of breast cancer by sponging miR‐135‐5p

Abstract

Circular RNAs have participated in oncology progress. Nevertheless, the potential mechanisms are not completely understood. We intended to inspect the functions of hsa_circ_0088088 on breast malignancy, together with the possible mechanism(s). hsa_-circ_0088088 expression in breast malignancy was studied using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). The overall survival was studied by the Kaplan-Meier curve. The biological functions of hsa_circ_0088088 aberrant expression on cell growth and metastasis were evaluated in MDA-MB-231 cells.Bioinformatics analysis, RNA immunoprecipitation (RIP), and qRT-PCR were accomplished to confirm the possible regulatory effects of eukaryotic initiation factor 4A3 (EIF4A3) on the biogenesis of hsa_circ_0088088. Furthermore, a dual-luciferase reporter assay, qRT-PCR, and RNA pull-down assay were used to confirm the association between the hsa_circ_0088088 and miR-135-5p in MDA-MB-231 cells. hsa_circ_0088088 was upregulated in the tumor tissues and cells, and higher expression presented an unfavorable prognosis. hsa_circ_0088088 overexpression promoted cell growth and metastasis in MDA-MB-231 cells. EIF4A3 was found to positively regulate hsa_circ_0088088. Furthermore, we confirmed that hsa_circ_0088088 sponges miR-135-5p and directly targets miR-135-5p with respect to the cell growth and metastasis in MDA-MB-231 cells. Our data suggest that EIF4A3-induced hsa_circ_0088088 stimulates the carcinogenic effects of breast tumors by sponging miR-135-5p.

The Exon Junction Complex component EIF4A3 plays a splicing-linked oncogenic role in Pancreatic Ductal Adenocarcinoma

“…Likewise, EIF4A3 silencing blunted tumor growth in a preclinical model (MIAPaCa-2 derived xenografted mouse). Our results are in close agreement with recent reports showing that targeting EIF4A3 can reduce tumor growth or aggressiveness features in other cancer types [30][31][32][43][44][45], reviewed in [18], thereby leveraging its potential as an actionable target in cancer.…”

“…However, few studies have explored EIF4A3 in PDAC and were focused on its interaction with other molecular players [27, 28]. In contrast, a growing number of studies are providing detailed experimental support for a relevant role of EIF4A3 in various cancers, including hepatocellular carcinoma [30], breast cancer [31] cervical cancer [32] or glioblastoma [43, 44] (reviewed in [18]). Although the underlying mechanisms proposed to mediate EIF4A3 differ for each tumor type investigated, there is a common trend involving RNA-related molecules and processes [18].…”

“…While it was proposed that the detection of autoantibodies to DDX48 could help improve PDAC diagnosis, no further reports confirmed or extended this idea. In other cancers, EIF4A3 has been found to be dysregulated and to play an oncogenic role and its underlying mechanisms have been examined [30][31][32]. Recently, we and others reported a profound alteration of key components of the splicing machinery in PDAC, with pathological implications [7][8][9][10][11].…”

CircCEP85 upregulates IGF1 expression to promote breast cancer progression via sponging miR-1193

“…CircRNA has a stable structure and is not easily degraded by various factors, and has tissue and disease specificity [7]. Growing evidence has demonstrated that cir-cRNAs ate involved in the progression many of cancers [8][9][10], including breast cancer [11]. For instance, cir-cRNA circWHSC1 was highly expressed and promoted the growth, metastasis and glycolysis of BC cells through regulating miR-212-5p and AKT3 [12].…”