Journal Article

LINC02154 promotes cell cycle and mitochondrial function in oral squamous cell carcinoma

Ogawa, Toshifumi, Sato, Tatsuya, Toyota, Mutsumi, Ishiguro, Kazuya, Suzuki, Hiromu, Ohguro, Hiroshi, Tohse, Noritsugu, Nojima, Iyori, Kitajima, Hiroshi, Kai, Masahiro, Miyazaki, Akihiro, Furuhashi, Masato, Yamamoto, Eiichiro, Yorozu, Akira, Sekiguchi, Shohei, Niinuma, Takeshi, Hatanaka, Yui

2025

Overview

Long noncoding RNAs (lncRNAs) play pivotal roles in the development of human malignancies, though their involvement in oral squamous cell carcinoma (OSCC) remains incompletely understood. Using The Cancer Genome Atlas (TCGA) dataset, we analyzed expression of 7840 lncRNAs in primary head and neck squamous cell carcinoma (HNSCC) and found that upregulation of LINC02154 is associated with a poorer prognosis. LINC02154 knockdown in OSCC cell lines induced cell cycle arrest and apoptosis, and significantly attenuated tumor growth in vitro and in vivo. Notably, depletion of LINC02154 downregulated FOXM1, a master regulator of cell cycle‐related genes. RNA pulldown and mass spectrometry analyses identified a series of proteins that could potentially interact with LINC02154, including HNRNPK and LRPPRC. HNRNPK stabilizes FOXM1 expression by interacting with the 3′‐UTR of FOXM1 mRNA, which suggests LINC02154 and HNRNPK promote cell cycling by regulating FOXM1 expression. Additionally, LINC02154 positively regulates HNRNPK expression by inhibiting microRNAs targeting HNRPNK. Moreover, LINC02154 affects mitochondrial function by interacting with LRPPRC. Depletion of LINC02154 suppressed expression of mitochondrial genes, including MTCO1 and MTCO2, and inhibited mitochondrial respiratory function in OSCC cells. These results suggest that LINC02154 exerts its oncogenic effects by modulating the cell cycle and oxidative phosphorylation in OSCC, highlighting LINC02154 as a potential therapeutic target. LINC02154 is frequently overexpressed in oral squamous cell carcinoma (OSCC) cells. By interacting with the RNA binding protein HNRNPK, LINC02154 stabilizes FOXM1, a key regulator of cell cycle‐related genes, thereby promoting cell cycle progression. Additionally, LINC02154 interacts with LRPPRC, which plays a role in regulating the transcription and stability of mitochondrial RNA, and modulates mitochondrial respiratory function.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: 3' Untranslated regions / Animals / Apoptosis / Apoptosis - genetics / Cancer / Carcinoma, Squamous Cell - genetics / Carcinoma, Squamous Cell - pathology / Cell cycle / Cell Cycle - genetics / Cell Cycle Checkpoints - genetics / cell cycle regulation / Cell growth / Cell Line, Tumor / Cell Proliferation - genetics / Chemotherapy / Electron transport / Female / Forkhead Box Protein M1 - genetics / Forkhead Box Protein M1 - metabolism / Gene expression / Gene Expression Regulation, Neoplastic / Genes / Genetic aspects / Genomes / Genomics / Head and neck carcinoma / Health aspects / Heterogeneous-Nuclear Ribonucleoprotein K - genetics / Heterogeneous-Nuclear Ribonucleoprotein K - metabolism / Humans / lncRNA / Male / Malignancy / Mass spectrometry / Mass spectroscopy / Mice / MicroRNA / MicroRNAs / MicroRNAs - genetics / miRNA / Mitochondria / Mitochondria - genetics / Mitochondria - metabolism / mitochondrial function / Mouth Neoplasms - genetics / Mouth Neoplasms - metabolism / Mouth Neoplasms - pathology / mRNA / Non-coding RNA / oral cancer / Oral carcinoma / Oral squamous cell carcinoma / Original / ORIGINAL ARTICLE / Oxidative phosphorylation / Prognosis / Proteins / RNA binding protein / RNA, Long Noncoding - genetics / RNA, Long Noncoding - metabolism / Software / Squamous cell carcinoma / Squamous Cell Carcinoma of Head and Neck - genetics / Squamous Cell Carcinoma of Head and Neck - metabolism / Squamous Cell Carcinoma of Head and Neck - pathology / Survival analysis / Therapeutic targets / Tongue / Tumor cell lines / Tumors / X chromosomes