Novel Role of Long Non-Coding RNA ASAP1-IT1 in Progression of Hepatocellular Carcinoma

Abstract

The long non-coding RNA (lncRNA) ASAP1-IT1 has been recently shown to aberrantly increase in ovarian and bladder cancer, while its role in other malignancies remains unexplored. This study was to characterize the expression and assess the potential role of ASAP1-IT1 in hepatocellular carcinoma (HCC). Fifty-four paired HCC and histologically normal tissues were obtained from HCC patients. Human HCC cell lines (HepG2, Huh7, SMMC-7721, and BEL-7402) and a normal liver cell line (LO2) were used for in vitro studies. ASAP1-IT1-specific siRNAs were used to silence ASAP1-IT1 expression, while the pcDNA-ASAP1-IT1 vector was constructed to up-regulate its expression. In situ hybridization and qRT-PCR were performed to characterize subcellular localization and expression of ASAP1-IT1. Cell proliferation and migration assays were conducted to examine the role of ASAP1-IT1 in the progression of HCC. In silico analysis was conducted to predict putative miRNA binding sites, which were validated by luciferase reporter assays. ASAP1-IT1 levels were significantly increased in HCC tissues and cells compared with controls. Notably, higher ASAP1-IT1 levels were significantly associated with poorer prognosis of HCC patients. In situ hybridization analysis revealed that ASAP1-IT1 was mainly localized in the nucleus of hepatoma cells and differentially expressed in trabecular, compact, and pseudoglandular forms of liver cancer. Furthermore, knockdown of ASAP1-IT1 significantly suppressed cell proliferation and migration, while its overexpression significantly promoted cell proliferation and migration of HCC cells. Mechanistically, ASAP1-IT1 might exert its role in HCC progression, at least in part, by directly interacting with miR-221-3p. In conclusion, ASAP1-IT1 is abnormally elevated in HCC, and higher levels are correlated with poorer prognosis. An underlying mechanism has been proposed for ASAP1-IT1-associated promotion of proliferation and migration in HCC cells. These findings have provided evidence supporting the oncogenic role of ASAP1-IT1 in HCC.

Inhibition of hepatocellular carcinoma growth via modulation of the miR-221/SOX11 axis by curcumin and berberine

“…It also acts as a biomarker of HCC and mediates its progression ( Huang et al, 2021a ). The significant downregulation of miR-221 following CUR and BBR treatment, as well as the enhanced effect of CUR-BBR combination therapy, suggests a pivotal role of miR-221 in the inhibitory effects of CUR-BBR on HCC progression, which is consistent with a previous study ( Liu et al, 2022a ). Importantly, our results showed that miR-221 overexpression partially reversed the CUR-BBR-mediated decrease in HEPG2 and Huh7 cell survival, which is the first confirmation that the anticancer effect of CUR-BBR is mediated by the miR-221 pathway.…”

Targeting Non-Coding RNAs for the Development of Novel Hepatocellular Carcinoma Therapeutic Approaches

“…lncRNA ASAP1-IT1 (the intronic transcript 1 (IT-1) of ArfGAP with SH3 domain, ankyrin repeat and PH domain 1 (ASAP1)) is known to correlate with the overall survival of ovarian cancer patients [78]. Liu et al [67] reported lncRNA ASAP1-IT1 upregulation in HCC tissue samples (54 patients) compared to matched histologically normal liver tissues. Moreover, an inverse correlation between lncRNA ASAP1-IT1 levels and patient overall survival was observed.…”