KEY TAKEAWAYS
- The study aimed to investigate how lncRNA ZFAS1 regulates ATIC transcription and affects patients with HCC progression via the PI3K/AKT pathway.
- Researchers noticed that lncRNA ZFAS1 promotes HCC cell proliferation and migration by activating the PI3K/AKT pathway.
Long noncoding RNAs (lncRNAs) significantly influence various cancer-related processes through their intricate interactions with RNAs. Among these, lncRNA ZFAS1 has been implicated in oncogenic roles in multiple cancer types. Nevertheless, the intricate biological significance and underlying mechanism of ZFAS1 in the initiation and progression of patients with hepatocellular carcinoma (HCC) remain largely unexplored.
Baoyang Luo and the team aimed to focus on investigating the role of lncRNA ZFAS1 in HCC, particularly how it regulates ATIC transcription and affects the proliferation and migration of HCC cells through the PI3K/AKT signaling pathway.
They performed an inclusive analysis of The Cancer Genome Atlas Program (TCGA) database, revealing a notable upregulation of lncRNA ZFAS1 in HCC tissues. Colony formation and CCK-8 assays were conducted to explore their function to gauge cellular proliferation, while wound healing and Transwell assays were used to assess cellular migration.
The vivo study employing a nude mouse model was carried out to scrutinize tumor growth and metastasis. A luciferase reporter assay was used to confirm the implicated interactions. Additionally, rescue experiments were conducted to unravel the plausible mechanism underlying the activation of the PI3K/AKT pathway by lncRNAs ZFAS1 and ATIC.
Analysis showed that ZFAS1 and ATIC were significantly upregulated in the HCC tissues and cells. ZFAS1 knockdown inhibited cell proliferation and migration. They observed a direct interaction between the lncRNA ZFAS1 and ATIC. ATIC knockdown also suppressed cell proliferation and migration.
SC79, an activator of AKT, partially restores the effects of lncRNA ZFAS1/ATIC knockdown on cell proliferation and migration. Knockdown of lncRNA ZFAS1/ATIC inhibited tumor growth and lung metastasis in vivo.
The study concluded that lncRNA ZFAS1 plays a pivotal role in regulating ATIC transcription, thereby promoting the growth and migration of HCC cells through activation of the PI3K/AKT signaling pathway.
This study was funded by the Young Talent Development Plan of the Changzhou Health Commission (CZQM2021028), and the Science and Technology Project of the Changzhou Health Commission (QN202338).
Source: https://pubmed.ncbi.nlm.nih.gov/39001904/
Luo B, Zhuang L, Huang J, et al. (2024). “LncRNA ZFAS1 regulates ATIC transcription and promotes the proliferation and migration of hepatocellular carcinoma through the PI3K/AKT signaling pathway.” J Cancer Res Clin Oncol. 2024 Jul 13;150(7):351. doi: 10.1007/s00432-024-05877-1. PMID: 39001904; PMCID: PMC11246283.
