Wu Jie, Chen Qiwen, Wang Yunliang, Wang Ruoqin, Chen Qing, Wang Yuhan, Qi Xin, Gao Yuan, Chen Kai
Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Minimally Invasive Therapy Center, Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
J Gastrointest Oncol. 2024 Feb 29;15(1):271-285. doi: 10.21037/jgo-24-52. Epub 2024 Feb 28.
How colorectal cancer (CRC) gain the ability to growth and metastasis remains largely unknown. Findings from preceding studies have revealed the participation of long non-coding RNAs (lncRNAs) in CRC progression. However, the role of LINC01977 in CRC remains unexplored. This study aims to explore the function and underlying mechanism of LINC01977 in CRC.
The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to analyze the expression of LINC01977 in CRC and its correlation with CRC prognosis. In our research, we explored the influence of LINC01977 on CRC progression such as cell proliferation, migration, invasion, and aerobic glycolysis, and identified its fundamental molecular mechanism using CRC cell lines and in vivo mouse xenograft models.
LINC01977 exhibited significantly elevated expression in CRC tissues and cell lines, and its level was significantly correlated with malignant clinicopathological characteristics and negative prognosis. Furthermore, both and tests revealed LINC01977's role in facilitating CRC cell proliferation and metastasis. LINC01977's significant part in CRC aerobic glycolysis was also discovered. With an aim to uncover the underlying mechanism, we investigated LINC01977's effect on c-Myc, a key gene in glycolysis. The results showed that LINC01977 regulated c-Myc stability via extracellular signal-regulated kinase (ERK)-mediated phosphorylation, and LINC01977-mediated c-Myc activated the level of vital glycolysis-related genes such as , and . Rescue experiments further confirmed that LINC01977 promoted CRC proliferation, metastasis, and aerobic glycolysis via c-Myc.
This study is the first to report that LINC01977 facilitates CRC proliferation, metastasis, and aerobic glycolysis through c-Myc, suggesting its potential as a therapeutic target for CRC treatment.
结直肠癌（CRC）如何获得生长和转移能力在很大程度上仍不清楚。先前研究的结果揭示了长链非编码RNA（lncRNAs）参与CRC进展。然而，LINC01977在CRC中的作用仍未被探索。本研究旨在探讨LINC01977在CRC中的功能及潜在机制。
利用癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）数据集分析LINC01977在CRC中的表达及其与CRC预后的相关性。在我们的研究中，我们利用CRC细胞系和体内小鼠异种移植模型探讨了LINC01977对CRC进展（如细胞增殖、迁移、侵袭和有氧糖酵解）的影响，并确定其基本分子机制。
LINC01977在CRC组织和细胞系中表达显著升高，其水平与恶性临床病理特征及不良预后显著相关。此外，实验和测试均揭示了LINC01977在促进CRC细胞增殖和转移中的作用。还发现LINC01977在CRC有氧糖酵解中起重要作用。为了揭示潜在机制，我们研究了LINC01977对糖酵解关键基因c-Myc的影响。结果表明，LINC01977通过细胞外信号调节激酶（ERK）介导的磷酸化调节c-Myc的稳定性，LINC01977介导的c-Myc激活了诸如、和等重要糖酵解相关基因的水平。挽救实验进一步证实LINC01977通过c-Myc促进CRC增殖、转移及有氧糖酵解。
本研究首次报道LINC01977通过c-Myc促进CRC增殖、转移及有氧糖酵解，提示其作为CRC治疗靶点的潜力。
