Circadian rhythm-based prognostic features predict immune infiltration and tumor microenvironment in molecular subtypes of hepatocellular carcinoma

基于昼夜节律的预后特征可预测肝细胞癌分子亚型中的免疫浸润和肿瘤微环境

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Abstract

Hepatocellular carcinoma (HCC) poses a significant threat to human health. Tumor microenvironment alterations, particularly immune-related changes, play a pivotal role in HCC progression, with high-throughput technologies facilitating the exploration of these dynamics. This study aimed to investigate the role of long non-coding RNA (lncRNA) AC019080.1 in HCC cells. A total of 24 circadian rhythm-related (CRR) messenger RNAs (mRNAs) and 433 CRR-lncRNAs were identified. Among them, 46 prognostically relevant circadian rhythm-related lncRNAs (PCRR-lncRNAs) were found to be upregulated in the HCC group. Molecular clustering analysis of 370 HCC samples revealed expression differences of PCRR-lncRNAs across three subtypes. Immune cell infiltration levels and tumor microenvironment analysis revealed significant subtype-specific differences. AC019080.1 and MCM3AP-AS1 were identified as core PCRR-lncRNAs in HCC, with elevated expression in both HCC tissues and cell lines. Through suppression of the Wnt/β-catenin signaling pathway, knockdown of lncRNA AC019080.1 significantly inhibited the proliferation, colony formation, migration, and invasion of HCC cells, while promoting apoptosis. This study suggests that circadian rhythm-related genes can predict immune infiltration and the molecular subtypes of HCC, providing valuable insights for diagnosis and treatment. lncRNA AC019080.1 holds potential as a therapeutic target for HCC.

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