HMGA2 regulates circular RNA ASPH to promote tumor growth in lung adenocarcinoma

Abstract

In this study, we identified a circular form of ASPH RNA (circASPH), expression of which was upregulated in lung adenocarcinoma and the human lung adenocarcinoma cell lines. We also found a positive correlation between circASPH level and the T and N stages of lung adenocarcinoma patients. Patients with higher levels of circASPH had a shorter overall survival. Moreover, we demonstrated that circASPH was directly regulated by HMGA2 and Twist1. The direct positive regulation of circASPH by Twist1 was dependent on the presence of HMGA2. Functional assays indicated that circASPH promoted the proliferation, migration, and invasion of lung adenocarcinoma cell lines in vitro. The promoting effect of tumor growth by circASPH was also observed in vivo. Mechanistically, circASPH was identified to act as a molecular sponge for miR-370 and abrogate miR-370-mediated inhibition of HMGA2. Finally, we demonstrated that the oncogenic function of circASPH was HMGA2-dependent. These findings reveal the oncogenic functions of the HMGA2-circASPH-HMGA2 axis and may be useful in developing circRNA-based therapeutic strategies for lung adenocarcinoma.

Characterization of the Relationship Between the Expression of Aspartate β-Hydroxylase and the Pathological Characteristics of Breast Cancer

“…ASPH has recently been shown to promote BC development and metastasis by activating the Notch cascade [ 11 ]. ASPH is also overexpressed and strongly correlated with tumor invasiveness and poor prognosis in various tumor types, including colorectal [ 12 ], hepatocellular [ 13 ], non-small cell lung [ 14 ], pancreatic [ 15 – 17 ], and prostate cancer [ 18 ], and cholangiocarcinoma [ 19 , 20 ].…”

CircEHD2, CircNETO2 and CircEGLN3 as Diagnostic and Prognostic Biomarkers for Patients with Renal Cell Carcinoma

“…The diagnostic relevance of circNETO2 may be limited as the diagnostic accuracy was moderate in our study (AUC = 0.705); circNETO2 has not been studied in RCC by other researchers so far. In lung cancer cells, circNETO2 expression was not different in normal and cancerous lung tissue [21].…”

A Novel circRNA–miRNA–mRNA Hub Regulatory Network in Lung Adenocarcinoma

“…Due to their stable structure, circRNAs are promised to become a new strategy for LUAD-targeted therapy. Xu et al observed that HMGA2 could regulate circASPH to promote tumor growth in patients with LUAD ( Xu L. et al, 2020 ). The study of Lu G.J.…”