Circ-ASH2L promotes tumor progression by sponging miR-34a to regulate Notch1 in pancreatic ductal adenocarcinoma

Abstract

BackgroundCircular RNAs (circRNAs) have recently been shown to play important roles in different tumors. However, their detailed roles and regulatory mechanisms in pancreatic ductal adenocarcinoma (PDAC) are not well understood. This study aimed to identify enriched circRNAs and detect their functions and mechanisms in PDAC cells and tissues.MethodscircRNA-ASH2L (circ-ASH2L) was identified by circRNA microarray studies based on previous studies, and further detected in PDAC cells and samples by qRT-PCR. The functions of circ-ASH2L were identified by transwell, EdU, cell cycle or Tube formation assays. The regulatory mechanisms of circ-ASH2L were explored by WB, RIP, FISH, dual-luciferase assays, RNA pulldown or other assays.ResultsWe identified a circRNA (circ-ASH2L) based on our previous studies, detected its expression in different malignant cells and found that circ-ASH2L was highly expressed in pancreatic cells or tumor tissues and correlated with tumor malignancy. Further studies revealed that circ-ASH2L promoted tumor invasion, proliferation and angiogenesis by regulating miR-34a, thus regulate Notch 1 expression. Circ-ASH2L served as a miRNA sponge for miR-34a and promoted tumor progression in vivo. Finally, we analyzed circ-ASH2L expression in clinical tissues and found that high circ-ASH2L expression was correlated with lymphatic invasion and TNM stage and was an independent risk factor for pancreatic patient survival.Conclusionscirc-ASH2L play an important role in tumor invasion, and high circ-ASH2L may be a useful marker of PDAC diagnosis or progression.

<p>CircHIPK3 Promotes Gemcitabine (GEM) Resistance in Pancreatic Cancer Cells by Sponging miR-330-5p and Targets RASSF1</p>

“…22,23 CircRNAs had been proved to be involved in the development, chemotherapy resistance, proliferation, invasion, and prognosis of PC. [24][25][26] In our study, the level of circHIPK3 was increased in PC tissues, GEMresistant PC tissues, and GEM-resistant PC cells. PC patients with high expression of circHIPK3 displayed poorer overall survival than those with lower circHIPK3 expression.…”

CircASH2L Promotes Ovarian Cancer Tumorigenesis, Angiogenesis, and Lymphangiogenesis by Regulating the miR-665/VEGFA Axis as a Competing Endogenous RNA

“…Meanwhile, KDR silencing by siRNA suppressed epithelial ovarian cancer invasion (Wang et al, 2009). Furthermore, Chen et al (2019) found that circ-ASH2L promoted tumor progression by sponging miR-34a to regulate Notch1 in pancreatic ductal adenocarcinoma. Whether miR-34a/Notch1 is also regulated by circASH2L in ovarian cancer needs further study.…”

“…Increasing evidence has shown that circRNAs, such as circASH2L (Chen et al, 2019), circHIPK3 (Wang et al, 2019b), circMET (Pei et al, 2020), circATXN1 (Liu X. et al, 2020), circZNF566 , circFMN2 (Shan et al, 2020), circCYFIP2 (Lin et al, 2020), and circWHSC1 (Zong et al, 2019), have essential functions in cancer biology and are potential biomarkers and treatment targets. We determined the expression of the eight star circRNAs in ovarian cancer and found that circASH2L was the only one expressed differently in our samples ( Figure 1A).…”

<p>Hsa_circ_0000069 Knockdown Inhibits Tumorigenesis and Exosomes with Downregulated hsa_circ_0000069 Suppress Malignant Transformation via Inhibition of STIL in Pancreatic Cancer</p>

“…Most circRNAs were reported to function as a ceRNA to sponge several miRNAs and suppress their activity. 30 CircRNAs via sponging the miRNAs could enhance the expression of the miRNA-targeted genes. 31 For example, circRNA-5692 can sponge miR-328-5p to enhance DAB2IP expression and the proliferation of hepatocellular carcinoma cells.…”