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

**Authors:** Jinhai Wang, Li Ma, Jinjuan Wang, Zhe Ma, Weiwei Wang, Songning Yu

PMC · DOI: 10.1515/biol-2025-1208 · Open Life Sciences · 2026-01-01

## TL;DR

This study explores how genes related to circadian rhythms can predict immune activity and cancer subtypes in liver cancer, offering new insights for diagnosis and treatment.

## Contribution

Identifies circadian rhythm-related lncRNAs as prognostic markers and immune predictors in hepatocellular carcinoma subtypes.

## Key findings

- 46 prognostically relevant circadian rhythm-related lncRNAs were identified in HCC.
- AC019080.1 and MCM3AP-AS1 are core lncRNAs associated with HCC progression and immune infiltration.
- Knockdown of AC019080.1 inhibits HCC cell proliferation and migration via Wnt/β-catenin pathway suppression.

## 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.

## Linked entities

- **Genes:** MCM3AP-AS1 (MCM3AP antisense RNA 1) [NCBI Gene 114044]
- **Diseases:** hepatocellular carcinoma (MONDO:0007256), HCC (MONDO:0007256)

## Full-text entities

- **Genes:** CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, MCM3AP-AS1 (MCM3AP antisense RNA 1) [NCBI Gene 114044] {aka C21orf85, MCM3AP-AS, MCM3APAS, MCM3APASB, NCRNA00031}
- **Diseases:** Tumor (MESH:D009369), HCC (MESH:D006528)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13011610/full.md

## References

48 references — full list in the complete paper: https://tomesphere.com/paper/PMC13011610/full.md

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Source: https://tomesphere.com/paper/PMC13011610